In the lower limbs, vasoconstriction triggered by venous distension and a local neural veni-arteriolar response is important for counteracting increases in capillary hydrostatic pressure during upright posture or limb dependency (Henriksen, 1991). In women, vasoconstriction in foot skin during leg dependency was attenuated in the luteal compared to follicular menstrual cycle phase, in association with increased fluid filtration which could contribute to premenstrual oedema (Hassan et al. 1990). Since leg dependency increases both arterial and venous hydrostatic pressures, it is not clear whether the smaller luteal vasoconstriction in women is due to a change in arterial myogenic constriction or the veni-arteriolar response. With local ethical committee approval, we studied vasoconstrictor responses to venous distension (thigh cuff inflation to 50 mmHg for 5 min) in 13 young women (age 24±4 years, height 161±2 cm, mean±S.D), 5 not taking (nonOC) and 8 taking (OC) oral contraceptives during follicular (days 10-13) and luteal (days 18-27) phases of the menstrual cycle, and in 7 young men (age 25±3 years, height 178±7 cm). After 5 min of venous distension, Laser Doppler skin perfusion in the foot dorsum decreased similarly from resting during both test phases in nonOC women (56±7% follicular, mean±S.E.M., 68±6% luteal, NS Wilcoxon signed ranks test) and OC women (51±3% follicular, 55±3% luteal, NS). Maximum vasoconstriction in men (46±9% after 5 min) was no different from either female group in either phase (one-way ANOVA), but its onset was delayed to the 2nd minute of distension whereas in all women, it occurred within the 1st minute. These data do not support a role for female hormone effects on the magnitude of the veni-arteriolar response. The gender difference in response latency may be related to disparate superficial venous filling times in men versus women. Veni-arteriolar vasoconstriction was also studied in the same groups in the calf, where venous distension occurs primarily in muscular rather than superficial vessels. Calf blood flow was measured using strain gauge plethysmography by brief thigh cuff inflations to 80-90 mmHg during venous distension (cuff at 50 mmHg for 5 min). After 1 min, blood flow decreased similarly in nonOC women (54±5% follicular, 54±8% luteal), OC women (54±5% follicular, 54±5% luteal) and men (52±3%). However, after 5 min, vasoconstriction in men had waned (16±5%) whereas in all women it had increased further (70%). This may be due to venous creep and relief of distension in men, relating to their greater calf venous compliance than women (Monahan & Ray, 2004). Locally mediated vasoconstriction in women may reduce their vasoconstrictor reserve and contribute to orthostatic intolerance.