The purpose of this study was to examine upper and lower limb vasoconstrictor responses to changes in transmural pressure in humans. Brachial and femoral blood mean blood velocity (MBV) and vessel diameter (Doppler ultrasound) were measured in 20 supine healthy subjects (10 men and 10 women; 27 +/- 1 yr; mean +/- SE) during four levels of limb suction at -25, -50, -75, and -100 mmHg, respectively. Limb suction led to an initial rise in MBV followed by a rapid fall in flow velocity to a level below MBV baseline, indicating a vasoconstriction effect. Femoral compared with brachial vessels exhibited a greater fall in flow velocity at all levels of suction (-89 +/- 17 vs. -10 +/- 2, -142 +/- 11 vs. -14 +/- 2, -156 +/- 22 vs. -13 +/- 2, and -162 +/- 29 vs. -12 +/- 2 ml/min for -25, -50, -75, and -100 mmHg, respectively; interaction effect, P < 0.05). Even at low tank suction levels (i.e., -10 and -20 mmHg), significant brachial flow velocity vasoconstriction from baseline values was demonstrated, reflecting downstream resistance vessel changes (n = 14). Brachial and femoral diameters did not change during changes in negative tank pressure. During suction, changes in limb volumes were significantly greater in the forearm (1.4 +/- 0.5%, 2.4 +/- 0.8%, 3.5 +/- 1.0%, and 4.3 +/- 1.1%) compared with the calf (0.9 +/- 0.5%, 1.4 +/- 0.7%, 2.0 +/- 0.8%, and 2.8 +/- 1.1%) at all levels of negative tank pressures (-25, -50, -75, and -100 mmHg, respectively). Simultaneous measurements of both upper limbs and both lower limbs suggested that the majority of the reduction in flow was due to myogenic influences except when -100 mmHg of suction was applied to the lower limb. The greater vasoconstriction responses in the leg compared with the arm with suction appear to be influenced by both myogenic and sympathetic mechanisms.