The present study examined the onset and the rate of rise of muscle oxidation during intense exercise in humans and whether oxygen availability limits muscle oxygen uptake in the initial phase of intense exercise. Six subjects performed 3 min of intense one-legged knee-extensor exercise [65.3 +/- 3.7 (means +/- SE) W]. The femoral arteriovenous blood mean transit time (MTT) and time from femoral artery to muscle microcirculation was determined to allow for an examination of the oxygen uptake at capillary level. MTT was 15.3 +/- 1.8 s immediately before exercise, 10.4 +/- 0.7 s after 6 s of exercise, and 4.7 +/- 0.5 s at the end of exercise. Arterial venous O(2) difference (a-v(diff) O(2)) of 18 +/- 5 ml/l before the exercise was unchanged after 2 s, but it increased (P <0.05) after 6 s of exercise to 43 +/- 10 ml/l and reached 146 +/- 4 ml/l at the end of exercise. Thigh oxygen uptake increased (P <0.05) from 32 +/- 8 to 102 +/- 28 ml/min after 6 s of exercise and to 789 +/- 88 ml/min at the end of exercise. The time to reach half-peak a-v(diff) O(2) and thigh oxygen uptake was 13 +/- 2 and 25 +/- 3 s, respectively. The difference between thigh oxygen delivery (blood flow x arterial oxygen content) and thigh oxygen uptake increased (P <0.05) after 6 s and returned to preexercise level after 14 s. The present data suggest that, at the onset of exercise, oxygen uptake of the exercising muscles increases after a delay of only a few seconds, and oxygen extraction peaks after approximately 50 s of exercise. The limited oxygen utilization in the initial phase of intense exercise is not caused by insufficient oxygen availability.