The present study examined whether an increase in leg blood flow and oxygen delivery at the onset of intense exercise would speed the rate of rise in leg oxygen uptake. Nine healthy men (25 ± 1 years old, mean ± SEM) performed one-leg knee-extensor exercise (62 ± 3 W, 86 ± 3% of incremental test peak power) for 4 min during a control setting (CON) and with infusion of ATP into the femoral artery in order to increase blood flow before and during exercise. In the presence of ATP, femoral arterial blood flow and O2 delivery were higher (P < 0.001) at the onset of exercise and throughout exercise (femoral arterial blood flow after 10 s, 5.1 ± 0.5 versus 2.7 ± 0.3 l min(-1); after 45 s, 6.0 ± 0.5 versus 4.1 ± 0.4 l min(-1); after 90 s, 6.6 ± 0.6 versus 4.5 ± 0.4 l min(-1); and after 240 s, 7.0 ± 0.6 versus 5.1 ± 0.3 l min(-1) in ATP and CON conditions, respectively). Leg oxygen uptake was not different in ATP and CON conditions during the first 20 s of exercise but was lower (P < 0.05) in the ATP compared with CON conditions after 30 s and until the end of exercise (30 s, 436 ± 42 versus 549 ± 45 ml min(-1); and 240 s, 705 ± 31 versus 814 ± 59 ml min(-1) in ATP and CON, respectively). Lactate release was lower after 60, 120 and 180 s of exercise with ATP infusion. These results suggest that O2 delivery is not limiting the rise in skeletal muscle oxygen uptake in the initial phase of intense exercise.