Isometric exercise training has been shown to reduce resting blood pressure, but the effect that this might have on orthostatic tolerance is poorly understood. Changes in orthostatic tolerance may also be dependent on whether the upper or lower limbs of the body are trained using isometric exercise. Twenty-seven subjects were allocated to either a training or control group. A training group first undertook 5 weeks of isometric exercise training of the legs, and after an 8 week intervening period, a second training group containing six subjects from the initial training group, undertook 5 weeks of isometric arm-training. The control group were asked to continue their normal daily activities throughout the 18 weeks of the study. In all subjects orthostatic tolerance, assessed using lower body negative pressure (LBNP), and resting blood pressure were measured before and after each of the 5 week training or control periods. Estimated lean leg volume was determined before and after leg-training. During all LBNP tests, heart rate and blood pressure were recorded each minute, and the time taken to reach the highest heart rate was derived (time to peak HR). Resting systolic blood pressure (mean ± S.D.), when measured during the last week of training, was significantly reduced after both leg (−10 ± 8.7 mmHg) and arm (−12.4 ± 9.3 mmHg; P<0.05) isometric exercise training, compared to controls. This reduction disappeared when blood pressure was measured immediately before the LBNP tests, which followed training. Orthostatic tolerance only increased after leg-training (20.8 ± 16.4 LTI; P<0.05) and was accompanied by an increased time to peak HR (119.8 ± 106.3 beats min−1; P<0.05) in this group. Blood pressure responses to LBNP did not change after arm-training, leg-training or in controls (P>0.05). There was a small but significant increase in estimated lean leg volume after leg-training (0.1 ± 0.1 l; P<0.05). These results suggest that lower resting blood pressure is probably not responsible for the increased orthostatic tolerance after isometric exercise training of the legs. Rather, it is possible that the training altered some other aspect of cardiovascular control during orthostatic stress that was apparent in the changes in heart rate. Legtraining was accompanied by increases in estimated lean leg volume. The effects of isometric training on orthostatic tolerance appear to be specific to limbs that are directly involved in LBNP testing.