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 minute one-legged knee-extensor exercise bout (24+/-1 (+/-S.D.) W) without (CON) and with (double blockade; DB) arterial infusion of inhibitors of nitric oxide synthase (NOS; L-NMMA) and cyclooxygenase (COX; indomethacin) in order to inhibit the synthesis of nitric oxide (NO) and prostanoids, respectively.. Leg blood flow and leg oxygen delivery throughout exercise was 25-50 % lower (P< 0.05) in DB compared to CON. Leg oxygen extraction (a-v O2 difference) was higher (P< 0.05) in DB than in CON (5 s: 127+/-3 vs. 56+/-4 ml l(-1)) 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(-1)). 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 NO appear to play important roles in elevating skeletal muscle blood flow in the initial phase of exercise. Key words: Oxygen delivery, oxygen extraction, nitric oxide, prostanoids.