Within the last decade huge advances have been made in the understanding of the interactions between the central nervous system (CNS) and the immune system. Foremost amongst these is the realization that cytokines, classically regarded as mediators and co-ordinators of the inflammatory and immune responses, can exert a number of neuromodulatory effects within the CNS under both physiological and pathological conditions (for recent reviews see Rothwell & Hopkins, 1995; Rothwell et al. 1997; Rothwell, 1999). Consistent with this, it has been shown that many cytokines and their receptors are present in the brain (Hopkins & Rothwell, 1995). Much attention has focused on the pro-inflammatory cytokine interleukin-1 (IL-1) especially the [beta] variant. IL-1[beta] has been shown to be produced in the CNS in response to a number of stimuli including peripheral administration of lipopolysaccharide (LPS); traumatic brain injury; acute stress; anorexia and [beta]-adrenoceptor agonist administration (e.g. Maruta et al. 1997). IL-1 receptors have also been shown to be present in many brain regions, with high levels in the hippocampus and hypothalamus (Ban et al. 1991). Expression of IL-1 receptors has also been shown to be upregulated in response to insult, e.g. kainic acid administration (Nishiyori et al. 1997) and expression is higher in aged animals (Murray & Lynch, 1998). However this review will concentrate on the effects of IL-1[beta] on hippocampal synaptic transmission and long-term potentiation (LTP), a process long thought to be an important underlying mechanism of learning and memory formation (for review see Bliss & Collingridge, 1993).

1.Tissues weighing from 0·006 to 3·0 g were dissected and put directly into 15 ml screw cap polypropylene tubes with a conical base (maximum of 3 g per tube). It proved unnecessary to mince tissue, even though smaller pieces may aid quicker digestion. Five millilitres of 2 M KOH in 99 % (IMS) ethanol with 0·5 % Tween-80 was then added. Tissue digestion was usually completed in 2-4 h using a dry heating block held at 60°C, with intermittent shaking. Samples were routinely processed using fresh tissues, although storage of frozen tissue (in the dark at -20°C) introduced no detectable error in BF estimation and tended to aid tissue maceration.2.After digestion was completed the tubes were centrifuged at 3000 r.p.m. (1500 g) for 15 min.3.The supernatant was carefully aspirated until < 500 µl was left, thereby reducing the possibility of accidental loss of microspheres.4.After 1 ml dH2O was added the tubes were quickly vortexed to prevent microsphere flocculation and aid resuspension of remaining pellets, while the subsequent addition of ethanoic Tween (100 % ethanol + 0·5 % Tween-80) allowed complete sedimentation by centrifugation.5.Nine millilitres of ethanoic Tween-80 was added, and the tubes were vortexed and spun at 1500 g for 15 min.6.The supernatant was aspirated as above (Step 3).7.Five millilitres of 100 mM phosphate buffer (pH 7·00) was added to neutralize the pellet as alkaline solutions quench fluorescence. Using aqueous solutions increased the possibility of microsphere loss by adhesion to the surface of tubes or aggregation, which could readily be seen by eye when tubes were examined under bright light, and hence the buffer was followed by addition of 4 ml absolute ethanol and further vortexing, before spinning (1500 g) for 20 min.8.The supernatant was aspirated, leaving up to 300 µl depending on the amount of tissue residue, and the remaining microspheres and pellet were quickly vortexed to ensure complete resuspension.9.The tubes were left to evaporate in an oven at 60°C and then briefly vortexed during this period to disperse more of the flocculent, until around 100 µl fluid remained. This improves solvent extraction of microspheres, which may be less efficient in a completely dry pellet.10.Two or three millilitres of solvent (di(ethylene glycol) ethyl ether acetate, 98 %; Aldrich Chemical Co., Poole, Dorset, UK) was added according to the expected fluorescence intensity, and vortexed several times over 3-5 min. After 30 min the tubes were sonicated in a water bath for 5 min to complete dye extraction by the solvent. The tubes were kept as far as possible in the dark after the solvent was added to avoid photo-bleaching of the fluorescent dyes.11.After sonication, the tubes were occasionally spun (1500 g) once more to sediment any undigested/undissolved material, though this was rarely necessary in our experiments. Readings should be completed within 1 h to avoid loss of signal intensity.

The effect of carbachol, an analogue of acetylcholine, on the delayed rectifier potassium current, iK, was investigated in rabbit isolated sino-atrial node cells using the whole cell patch clamp technique with amphotericin-permeabilized patches. In the presence of 500 nM atropine and 500 nM hexamethonium to block muscarinic and nicotinic receptors, respectively, 500 nM carbachol decreased the amplitude and rate of deactivation of iK without, however, affecting the slope of the iK activation curve. The same concentration of carbachol decreased the pacemaking rate of spontaneously active sino-atrial node cells by more than 13 %. Thus, there is a non-muscarinic and non-nicotinic pathway for cholinergically induced reduction in the amplitude and rate of deactivation of iK that would appear to contribute to negative chronotropy in rabbit sino-atrial node pacemaker cells.

Uridine triphosphate (UTP) evoked inhibition of adrenaline-evoked cAMP accumulation in cultured equine epithelial cells (EC50, 1á8 ± 0á2 µM) and this effect was mimicked by 5-Br-UTP (EC50, 6á6 ± 1á8 µM) and uridine diphosphate (UDP; EC50, 96 ± 26 µM). This inhibitory action of UTP was abolished by pre-treating cells with pertussis toxin (10 ng ml-1, 24 h). UTP (EC50, 2á3 ± 0á3 µM) and 5-Br-UTP (EC50, 29á4 ± 9á4 µM) also increased intracellular free calcium ([Ca2+]i) whilst UDP did not; the two effects are thus differentially sensitive to these pyrimidine nucleotides. ATP evoked cAMP accumulation in control cells and this response was unaffected by pertussis toxin. There is, therefore, no indication that ATP activates the pertussis toxin-sensitive inhibitory pathway. The UTP-evoked inhibition of cAMP accumulation was abolished by isobutylmethylxanthine (IBMX, 5 mM) and so the negative control over cAMP levels appears to be mediated by receptors that are selectively activated by pyrimidine nucleotides and permit control over phosphodiesterase activity.

In order to advance our understanding of the phenomenon of flow-induced increases in the metabolism of the relaxed muscle, the metabolic rate of the isolated rat gracilis muscle was investigated at 28¡C in vitro. The muscle was perfused with cell-free Krebs-Henseleit bicarbonate buffer containing 5 % bovine serum albumin and 5 mM glucose, saturated with a gas mixture of 95 % O2 and 5 % CO2 and simultaneously superfused with a medium saturated with a low O2 gas mixture (1 % O2, 5 % CO2 and 94 % N2). Two different perfusion flow rates (0á054 and 0á100 ml min-1) have been used. Their influence on oxygen consumption and lactate production has been measured. After a 100 min perfusion period, the muscle was freeze-clamped and analysed for ATP, phosphocreatine, creatine, lactate, pyruvate, inorganic phosphate and glycogen content. The energy state of the cell and the proportions of glycolytic and mitochondrial fluxes of ATP synthesis were evaluated. During perfusion at the low flow rate of 0á054 ml min-1, the oxygen uptake was 45 ± 9 nmol min-1 (g wet wt)-1, accompanied by a dominance of anaerobic glycolytic synthesis of ATP over mitochondrial ATP synthesis, even though the total delivery of oxygen to muscle was three times higher than oxygen consumption. Increasing the perfusion flow rate to 0á100 ml min-1 increased the oxygen uptake to 120 ± 6 nmol min-1 (g wet wt)-1, thus leading to a prevalence of mitochondrial ATP synthesis over glycolytic ATP synthesis. The inner stores of glycogen served as the main substrate of energy metabolism and the role of exogenous substrates in the flow-stimulated increase of oxygen uptake was negligible. The increase in perfusion rate also enhanced the energy state of the muscle fibres, which was expressed either as the creatine charge or as the value of the change of Gibbs free energy of ATP hydrolysis. Data indicate that the change of perfusion flow rate per se, apart from oxygen and exogenous substrate supply, elicits changes in the regulation of energy metabolism within non-contracting skeletal muscle under open microcirculation.

The motility of the reticulo-rumen has been measured in trained, conscious sheep using inflated balloons temporarily introduced to selected regions of that forestomach. The frequency and amplitude of the contractions of the reticulum and both the A and B waves of contraction of the rumen were measured under the same conditions before, during and after the administration of an I.V. bolus of either parathyroid hormone (PTH(1-34)) or PTH-related protein (PTHrP(1-34)) followed by its I.V. infusion. These two peptides are known to share a common receptor in other organs, e.g. the kidney. In this study they both showed an inhibitory effect on reticulo-ruminal motility. The effect of PTHrP(1-34) on the rate of ruminal blood flow was also examined and a significant reduction observed, after a transient increase. The secretion of endogenous PTH(1-34) was stimulated by a 32 % reduction in the plasma calcium ion concentration induced by an I.V. infusion of sodium citrate. Associated with this were significant reductions in reticulo-ruminal motility, e.g. the reduction in the mean amplitude of the reticular contractions reflected the reduction in plasma calcium ion concentration. When the PTH(1-34)/PTHrP(1-34) receptor was blocked with [Asn10,Leu11,D-Trp12]PTHrP(7-34) before and during the induction of hypocalcaemia, all but one of the parameters of reticulo-ruminal motility were normalized. Indeed, by the day following the administration of this blocking agent, all these parameters had returned to their normal range. It is concluded that stimulation of the PTH(1-34)/PTHrP(1-34) receptor in reticulo-ruminal smooth muscle reduces the motility of this tissue and may play a role in the depression of motility of the digestive tract which is characteristic of clinical milk fever in the dairy cow.

Submandibular secretory responses to stimulation of the parasympathetic chorda-lingual nerve were investigated in five anaesthetized cats before, during and after withdrawal of blood (ca 20 ml kg-1) in order to investigate the consequences of a reduced blood flow through the gland. Stimulation at different frequencies (2, 4, 6 and 8 Hz) evoked a frequency-dependent increase in the flow of submandibular saliva, sodium concentration, electrolyte and protein output. When the blood pressure was reduced (by about 50 %) there was a significant reduction in submandibular blood flow and the secretion of both saliva and protein during stimulation. Under each set of conditions the flow of saliva was linearly related to the blood flow through the gland. It is concluded that submandibular secretory responses to electrical stimulation of the parasympathetic innervation can be significantly attenuated when the blood flow through the gland is reduced under the conditions employed in this study.

This study was undertaken to improve the measurement of glomerular filtration rate (GFR) during the acute diuretic phase induced by atrial natriuretic peptide (ANP), which may indeed alter the renal clearance of inulin (GFRCL) due to dead space error. A technique to measure GFR without urine collections was therefore developed in anaesthetized rats prepared as for micropuncture. To do so, arterial blood was periodically collected and renal venous blood was withdrawn simultaneously from a catheter inserted into the left suprarenal vein to determine the renal extraction coefficient of inulin (CEIN). In addition, renal blood flow (RBF) was continuously measured with an electromagnetic flow transducer fitted around the left renal artery to estimate renal plasma flow (RPF). GFR (GFRCE) was then calculated as the product of RPF and CEIN. To study the effects of ANP on GFR, rats were injected I.V. with 10 µl of saline without (n = 6; vehicle) or with 1 µg ANP (n = 6; ANP) and GFRCE and GFRCL were compared before and after each treatment. They did not differ significantly during baseline measurements in each experimental group and were not modified after vehicle. Similarly, RBF remained constant. In contrast, RBF and GFRCE increased rapidly and simultaneously 90 s after ANP, from 9á07 ± 0á25 to 10á07 ± 0á35 (12 %) and from 1á209 ± 0á188 to 1á715 ± 0á190 ml min-1 (42 %), respectively (P < 0á05). GFRCL increased to an even greater extent (88 %). Moreover, the peak enhancement of GFRCL was delayed and occurred 180 s after ANP. The renal clearance of inulin was thus unduly elevated due to sudden changes in the dead space induced by the diuretic effect of ANP. In conclusion, determination of glomerular filtration rate by the method of renal extraction of inulin provided more reliable results than those achieved using the classical method of renal clearance of inulin. Moreover, it was sufficiently sensitive to detect small and transient changes in GFR induced by the injection of 1 µg ANP.

Plasma glucagon concentrations were measured in chronically catheterized fetal ponies and their mothers between 260 days of gestation and term (~ 335 days). Fetal [alpha] cell responses to arginine and variations in fetal glycaemia were also examined during late gestation. Immunoreactive glucagon was present in fetal plasma at 260 days of gestation and its concentration in utero increased after 320 days and then again at birth. Maternal plasma glucagon concentrations were higher after 300 days than earlier in gestation but were lower than the corresponding fetal value throughout the period of gestation studied. Fetal [alpha] cells responded rapidly to intravenous arginine infusion but not to changes in the fetal glucose level induced by maternal fasting for 36 h or by intrafetal infusion of glucose. The maximal increment in fetal plasma glucagon in response to arginine occurred at the end of the 5 min infusion and was positively correlated to the basal pre-infusion plasma glucagon concentrations. Fetal plasma glucagon concentrations were unaffected by either hyper- or hypoglycaemia. In contrast, maternal plasma glucagon levels were significantly increased by fasting. These observations indicate that equine pancreatic [alpha] cells are functional in utero but that they are unresponsive to variations in glycaemia until after birth.

In nine 2- to 3-month-old hyperketonaemic piglets the kinetics of glucose and D-[beta]-hydroxybutyrate (D-BHB) metabolism were studied during hypo- and normocalcaemia in paired experiments. Hyperketonaemia (1á3 and 2á5 mmol D-BHB (l plasma)-1) was generated by a stepwise increase of DL-BHB infusion. Hypocalcaemia spontaneously developed in five piglets due to an inherited calcitriol deficiency and was induced in four control piglets by a continuous infusion of Na2-EDTA. The method of single isotopic marker injections of glucose and D-BHB was used to calculate replacement rates, rate constants and half-lives of glucose and D-BHB in plasma. When DL-BHB was infused at the same rate into normo- and hypocalcaemic piglets, hypocalcaemia reduced the rate constant of glucose by 20-30 % and the replacement rate of glucose by 34 %. In the presence of hyperketonaemia, hypocalcaemia increased the rate of replacement of D-BHB by 6-40 %. The replacement rate represents the sum of endogenous production and the rate of DL-BHB infusion. This observation shows that the endogenous production of D-BHB was higher during hypocalcaemia than during normocalcaemia.

Lung liquid (LL) is secreted into the fetal lung lumen, but it must be rapidly absorbed at birth to allow air breathing. In vitro studies have implicated oxygen as a possible factor causing the switch from secretion to absorption of lung liquid at birth. We developed a technique of oxygenating the fetal lung using liquid ventilation with haemoglobin (Hb) solutions in chronically catheterized fetal lambs (129-140 days gestation; term, 147 days). In some experiments 2,3-diphosphoglycerate (DPG) was added to increase oxygen delivery. LL secretion rate (Jv) was measured using an indicator dilution method. Eighteen fetuses were divided into four groups and ventilated with liquid under the following conditions: (i) Hb with oxygen, (ii) Hb without oxygen, (iii) Hb with DPG and oxygen and (iv) Hb with DPG without oxygen. There was a significant rise (2á6 mmHg, P < 0á02) in fetal arterial PO2 in group iii, but in none of the other groups. In the first 3 h of liquid ventilation there was no difference in Jv between the groups. In group i, during hours 4-6 of liquid ventilation, there was a significant rise in secretion rate from 2á25 ± 0á88 to 3á74 ± 0á85 ml h-1 kg-1 (P < 0á001). In group iii, when comparing Jv in the first 3 h of liquid ventilation with that in the following 3 h period of liquid ventilation, a strong trend towards reduction in secretion was observed, falling from 3á03 ± 0á65 to 0á74 ± 0á92 ml h-1 kg-1 (three of the four experiments showed a significant decrease in Jv in hours 4-6). These experiments indicate that oxygen delivered to the fetus using liquid ventilation with haemoglobin solutions leads to increased LL secretion when oxygen delivery is small, and suggest there is a decrease in secretion with greater oxygen delivery to the lung.

A video-laryngoscopic method, implemented with an algorithm for the correction of the deformation inherent in the endoscope optical system, has been used to measure the dorsoventral diameter (Drg) and the cross-sectional area (CSArg) of the rima glottidis in five healthy workhorses during conscious breathing at rest. Simultaneous recording of the respiratory airflow was also obtained in two horses. Drg measured 82·7 ± 4·5 mm (mean ± S.D.) independently of the respiratory phase, and did not differ from the measurement in post-mortem anatomical specimens of the same horses. CSArg ranged from 1130 ± 117 mm2 (mean ± S.D.) during the inspiratory phase to 640 ± 242 mm2 during the expiratory phase, being always narrower than tracheal cross-sectional area, which was 1616 ± 224 mm2, as determined from anatomical specimens. Both inspiratory and expiratory airflow waves displayed a biphasic pattern. Maximal laryngeal opening occurred in phase with the second inspiratory peak, while during expiration CSArg attained a minimum value during the first expiratory peak which was significantly smaller (P < 0·01) than the area subsequently maintained during the rest of the expiratiory phase. These quantitative measurements of equine laryngeal movements substantiate the important role played by the larynx in regulating upper airway respiratory resistance and the expiratory airflow pattern at rest.

Cross-sectional studies have compared the oxygen uptake (VO2 ) kinetics during the on-transient of moderate intensity exercise in older and younger adults. The slower values in the older adults may have been due to an age-related reduction in the capacity for O2 transport or alternatively a reduced intramuscular oxidative capacity. We studied: (1) the effects of ageing on VO2 kinetics in older adults on two occasions 9 years apart, and (2) the effect of hyperoxia on VO2 kinetics at the second test time. After a 9 year period, follow-up testing was undertaken on seven older adults (78 ± 5 years, mean ± S.D.). They each performed six repeats of 6 min bouts of constant-load cycle exercise from loadless cycling to 80 % of their ventilatory threshold. They breathed one of two gas mixtures (euoxia: inspired O2 fraction, FI,O2, 0á21; hyperoxia: FI,O2, 0á70) on different trials determined on a random basis. Breath-by-breath VO2 data were time aligned and ensemble averaged. VO2 kinetics, modelled with a single exponential from phase 2 onset (+20 s) to steady state and described by the exponential time constant ([tau]) were compared with data collected from the same adults 9 years earlier. One-way repeated measures analysis of variance revealed that [tau] was slowed significantly with age (from 30 ± 8 to 46 ± 10 s), but was unaffected by hyperoxia (43 ± 15 s). We concluded that: (1) in older adults studied longitudinally over a 9 year period, the on-transient VO2 kinetics are slowed, in agreement with, but to a greater extent, than from cross-sectional data; and (2) the phase 2 time constant ([tau]) for these older adults was not accelerated by hyperoxic breathing. Thus the expected hyperoxia-induced increase in the capacity for O2 transport was not associated with faster on-transient VO2 kinetics suggesting either that O2 transport may not limit VO2 kinetics during the 8th decade, or that O2 transport was not improved with hyperoxia.

In order to test the hypothesis that glycogen sparing observed early during exercise following caffeine ingestion was a consequence of tighter metabolic control reflected in faster VO2 kinetics, we examined the effect of caffeine ingestion on oxygen uptake (VO2), carbon dioxide production (VCO2) and expiratory ventilation (VE) kinetics at the onset of both moderate (MOD) and heavy (HVY) intensity exercise. Male subjects (n = 10) were assigned to either a MOD (50 % VO2,max, n = 5) or HVY (80 % VO2,max, n = 5) exercise condition. Constant-load cycle ergometer exercise was performed as a step function from loadless cycling 1 h after ingestion of either dextrose (placebo, PLAC) or caffeine (CAFF; 6 mg (kg body mass)-1). Alveolar gas exchange was measured breath-by-breath. A 2- or 3-component exponential model, fitted through the entire exercise transient, was used to analyse gas exchange and ventilatory data for the determination of total lag time (TLT: the time taken to attain 63 % of the total exponential increase). Caffeine had no effect on TLT for VO2 kinetics at either exercise intensity (MOD: 36 ± 14 s (PLAC) and 41 ± 10 s (CAFF); HVY: 99 ± 30 s (PLAC) and 103 ± 26 (CAFF) (mean ± S.D.)). TLT for VE was increased with caffeine at both exercise intensities (MOD: 50 ± 20 s (PLAC) and 59 ± 21 s (CAFF); HVY: 168 ± 35 s (PLAC) and 203 ± 48 s (CAFF)) and for VCO2 during MOD only (MOD: 47 ± 14 s (PLAC) and 53 ± 17 s (CAFF); HVY: 65 ± 13 s (PLAC) and 69 ± 17 s (CAFF)). Contrary to our hypothesis, the metabolic effects of caffeine did not alter the on-transient VO2 kinetics in moderate or heavy exercise. VCO2 kinetics were slowed by a reduction in CO2 stores reflected in pre-exercise and exercise end-tidal CO2 pressure (PET,CO2) and plasma PCO2 which, we propose, contributed to slowed VE kinetics.

To study the effect of temperature on muscle metabolism during submaximal exercise, six endurance-trained men had one thigh warmed and the other cooled for 40 min prior to exercise using water-perfused cuffs. One cuff was perfused with water at 50-55¡C (HL) with the other being perfused with water at 0¡C (CL). With the cuffs still in position, subjects performed cycling exercise for 20 min at a work load corresponding to 70 % VO2,peak (where VO2,peak is peak pulmonary oxygen uptake) in comfortable ambient conditions (20-22¡C). Muscle biopsies were obtained prior to and following exercise and forearm venous blood was collected prior to and throughout the exercise period. Muscle temperature (Tmus) was not different prior to treatment, but treatment resulted in a large difference in pre-exercise Tmus (difference = 6á9 ± 0á9¡C; P < 0á01). Although this difference was reduced following exercise, it was nonetheless significant (difference = 0á4 ± 0á1¡C; P < 0á05). Intramuscular [ATP] was not affected by either exercise or muscle temperature. [Phosphocreatine] decreased (P < 0á01) and [creatine] increased (P < 0á01) with exercise but were not different when comparing HL with CL. Muscle lactate concentration was not different prior to treatment nor following exercise when comparing HL with CL. Muscle glycogen concentration was not different when comparing the trials before treatment, but the post-exercise value was lower (P < 0á05) in HL compared with CL. Thus, net muscle glycogen use was greater during exercise with heating (208 ± 23 vs. 118 ± 22 mmol kg-1 for HL and CL, respectively; P < 0á05). These data demonstrate that muscle glycogen use is augmented by increases in intramuscular temperature despite no differences in high energy phosphagen metabolism being observed when comparing treatments. This suggests that the increase in carbohydrate utilization occurred as a direct effect of an elevated muscle temperature and was not secondary to allosteric activation of enzymes mediated by a reduced ATP content.

One of the earliest events in the formation of an atherosclerotic lesion is the adherence of circulating monocytes to the vascular endothelium, through which they then gain entry to the sub-intimal tissue. This early lesion subsequently evolves over a number of years to form an atherosclerotic plaque, through the migration and proliferation of cells, the accumulation of lipid in the vessel wall and through the extensive deposition and modification of a connective tissue matrix. Pathological studies have described a wide spectrum of structural architecture in atherosclerotic plaques which suggests that, with time, the vascular connective tissue matrix is extensively modified during atherogenesis. This process of vascular connective tissue remodelling, where matrix macromolecules are both deposited and degraded, is controlled by a complex network of cell-cell and cell-matrix interactions, involving the secretion of a wide variety of growth factors and cytokines and chemokines.

We discovered in 1987 that the shorter form of apolipoprotein B (B48) synthesized in the intestine is due to the action, previously unrecognized in mammalian cells, of an mRNA-editing process, and more recently we demonstrated that this was due to a specific enzyme (APOBEC-1) with cytidine deaminase activity. We show here, by sequence alignment, molecular modelling and mutagenesis, that APOBEC-1 is a cytidine deaminase, responsible for editing apoB mRNA, and that is related in crystal structure to the cytidine deaminase of Escherichia coli (ECCDA). The two enzymes are both homodimers with composite active sites formed with loops from each monomer. In the sequence of APOBEC-1, three gaps compared with ECCDA match the size and contour of the minimal RNA substrate. We propose a model in which the asymmetric binding of one active site to the substrate cytidine which is positioned by the downstream binding of the product uridine and that this helps to target the other active site for deamination.

Presented at the Cambridge Meeting of the Society in December 1997 This symposium paper has already been published as a Review Article in Experimental Physiology, volume 83, pp. 573-584.

As skeletal muscle fibres mostly express a single myosin isoform, they are a potential source of pure myosin isoforms. A technique is described that allows extraction and identification of pure myosin isoforms from single fibres, and testing of such myosins in an in vitro motility assay (IVMA). The results show that the extraction procedure does not alter myosin function and support the view that single fibres are reliable sources of purified myosin isoforms for IVMA.

The thresholds for detection of a tremor-like movement are described. Detection is poorest at frequencies which correspond to natural tremor. The results are in accord with the failure of persons often to notice that their hands are tremulous.