Past studies have found that total-body O2 extraction during hypoxia was less in 1-wk-old lambs than in older animals. It was proposed that reduced O2 extraction was secondary to suppression of growth-related oxygen consumption (VO2) in tissues such as skeletal muscle, bone, kidney, and skin, rather than a defect in peripheral O2 use. To determine the capacity of immature skeletal muscle to extract O2, we isolated the hind limb circulation of eight ketamine-anesthetized, 7- to 18-d-old lambs exposed to stagnant hypoxia by inflation of a right atrial balloon catheter. Femoral arterial and venous PO2, PCO2, pH, Hb concentration, O2 saturation, and femoral arterial blood flow (Q) were measured and hind limb O2 delivery (DO2), extraction ratio, and VO2 calculated. Individual critical levels of DO2 below which VO2 was dependent on O2 supply were determined by dual-line best-fit regression analysis. In six of eight animals, VO2 was clearly independent of supply until DO2 reached critically low levels. However, O2 extraction during extreme hypoxia appeared submaximal (baseline O2 extraction ratio, 0.22 +/- 0.06; at critical levels of DO2, 0.51 +/- 0.11; at the lowest level of Q, 0.64 +/- 0.15). When 2,4-dinitrophenol, an uncoupler of oxidative phosphorylation, was administered to four additional lambs exposed to stagnant hypoxia, O2 extraction below critical levels of DO2 increased from 0.48 +/- 0.15 to 0.79 +/- 0.10 (p less than 0.001, unpaired t test). These data suggest that initial limitations in O2 extraction were a result of the suspension of O2-consuming processes, not an irreversible defect in peripheral O2 use.