This study examined the time course of changes in blood flow to the lower leg in response to venous distension – the veni-arteriolar vasoconstrictor response – in 31 healthy males. During a 5-min period of venous distension (thigh cuff pressure 50 mm Hg), calf blood flow (venous occlusion plethysmography) decreased more rapidly (within 30 s) compared to skin perfusion (after 2 min, Laser Doppler flowmetry), consistent with disparate filling times of superficial and deeper veins and a greater increase in deep vein volume. On completion of venous filling, vascular resistance in the skin was unchanged from baseline, implying that the reduction in perfusion was solely the result of reduced perfusion pressure. For the whole calf, vascular resistance was unchanged after 1 min but decreased thereafter by 35–45% from baseline, indicating adjustment of pre- or post-capillary resistances to maintain flow. Repeated plethysmographic flow measurements assisted the decrease in resistance, most likely by intermittent compression of the thigh cuff acting to displace blood volume centrally and alleviate congestion. These findings do not support an active veni-arteriolar vasoconstrictor mechanism in response to venous distension alone in the lower leg, and provide evidence of dynamic flow adjustments that should be acknowledged during procedures that involve prolonged periods of venous congestion.