We tested the hypothesis that the slower increase in alveolar oxygen uptake (V˙o 2) at the onset of supine, compared with upright, exercise would be accompanied by a slower rate of increase in leg blood flow (LBF). Seven healthy subjects performed transitions from rest to 40-W knee extension exercise in the upright and supine positions. LBF was measured continuously with pulsed and echo Doppler methods, andV˙o 2 was measured breath by breath at the mouth. At rest, a smaller diameter of the femoral artery in the supine position ( P < 0.05) was compensated by a greater mean blood flow velocity (MBV) ( P < 0.05) so that LBF was not different in the two positions. At the end of 6 min of exercise, femoral artery diameter was larger in the upright position and there were no differences inV˙o 2, MBV, or LBF between upright and supine positions. The rates of increase ofV˙o 2 and LBF in the transition between rest and 40 W exercise, as evaluated by the mean response time (time to 63% of the increase), were slower in the supine [V˙o 2 = 39.7 ± 3.8 (SE) s, LBF = 27.6 ± 3.9 s] than in the upright positions (V˙o 2 = 29.3 ± 3.0 s, LBF = 17.3 ± 4.0 s; P < 0.05). These data support our hypothesis that slower increases in alveolarV˙o 2 at the onset of exercise in the supine position are accompanied by a slower increase in LBF.