In response to hypoxic breathing most studies report slower pulmonary oxygen uptake (Vo(2)) kinetics at the onset of exercise, but it is not known if this relates to an actual slowing of the Vo(2) in the active muscles(.) The aim of the present study was to evaluate whether thigh Vo(2) is slowed at the onset of intense exercise during acute exposure to hypoxia. Six healthy male subjects (25.8 ± 1.4 yr, 79.8 ± 4.0 kg, means ± SE) performed intense (100 ± 6 watts) two-legged knee-extensor exercise for 2 min in normoxia (NOR) and hypoxia [fractional inspired oxygen concentration (Fi(O(2))) = 0.13; HYP]. Thigh Vo(2) was measured by frequent arterial and venous blood sampling and blood flow measurements. In arterial blood, oxygen content was reduced (P <0.05) from 191 ± 5 ml O(2)/l in NOR to 180 ± 5 ml O(2)/l in HYP, and oxygen pressure was reduced (P <0.001) from 111 ± 4 mmHg in NOR to 63 ± 4 mmHg in HYP. Thigh blood flow was the same in NOR and HYP, and thigh oxygen delivery was consequently reduced (P <0.05) in HYP, but femoral arterial-venous oxygen difference and thigh Vo(2) were similar in NOR and HYP. In addition, muscle lactate release was the same in NOR and HYP, and muscle lactate accumulation during the first 25 s of exercise determined from muscle biopsy sampling was also similar (0.35 ± 0.07 and 0.36 ± 0.07 mmol·kg dry wt(-1)·s(-1) in NOR and HYP). Thus the increase in thigh Vo(2) was not attenuated at the onset of intense knee-extensor exercise despite a reduction in oxygen delivery and pressure.