The activation of cardiovascular reflexes for postural adaptation questions whether, in healthy humans, the central blood volume is optimised to support the upright position. A functional definition of an 'optimal circulating volume' that provides the heart with enough central blood volume to establish a maximal cardiac output (CO) and mixed venous oxygen saturation (Sv,O2) at rest was evaluated in nine healthy subjects. Preload to the heart was varied by passively changing the body position from 70 deg head-up to 20 deg head-down tilt. The Sv,O2 was compared with simultaneously measured estimates of CO by computer-controlled thermodilution. The CO was in the range 8.7-3.8 l min-1 and Sv,O2 was in the range 79-58 %. Neither CO (median 6.0 (range 5.3-8.7) l min-1) nor Sv,O2 (mean ± S.D. 73.6 ± 2.6 %) changed from the supine to the 20 deg head-down position. During sustained 70 deg head-up tilt, Sv,O2 decreased to 64 ± 4 % together with a decline in CO to 4.7 (3.9-5.6) l min-1 (P < 0.05). Under conditions of varying tilt angles, a change in CO is paralleled by concordant changes in Sv,O2. Maximal values for CO and Sv,O2 during supine rest suggest that the horizontal position provides for an 'optimal' central blood volume. Experimental Physiology (2003) 88.5, 611-616.