The effect of low blood flow at onset of moderate-intensity exercise on the rate of rise in muscle oxygen uptake was examined. Seven male subjects performed a 3.5-min one-legged knee-extensor exercise bout (24 +/- 1 W, mean +/- SD) without (Con) and with (double blockade; DB) arterial infusion of inhibitors of nitric oxide synthase (N(G)-monomethyl-l-arginine) and cyclooxygenase (indomethacin) to inhibit the synthesis of nitric oxide and prostanoids, respectively. Leg blood flow and leg oxygen delivery throughout exercise was 25-50% lower (P < 0.05) in DB compared with Con. Leg oxygen extraction (arteriovenous O(2) difference) was higher (P < 0.05) in DB than in Con (5 s: 127 +/- 3 vs. 56 +/- 4 ml/l), and leg oxygen uptake was not different between Con and DB during exercise. The difference between leg oxygen delivery and leg oxygen uptake was smaller (P < 0.05) during exercise in DB than in Con (5 s: 59 +/- 12 vs. 262 +/- 39 ml/min). The present data demonstrate that muscle blood flow and oxygen delivery can be markedly reduced without affecting muscle oxygen uptake in the initial phase of moderate-intensity exercise, suggesting that blood flow does not limit muscle oxygen uptake at the onset of exercise. Additionally, prostanoids and/or nitric oxide appear to play important roles in elevating skeletal muscle blood flow in the initial phase of exercise.