Rates of O2 uptake across isolated perfused skin of bullfrogs (Rana catesbeiana) were measured in relation to blood flow at three levels of ambient O2 tension: normoxia (O2 tension = 152 torr), hypoxia (12% O2, 87 torr) and hyperoxia (42% O2, 306 torr). At bulk perfusion rates ranging from 3.4 to 10.1 microliters.cm-2 x min-1, O2 uptake was positively correlated with hemoglobin delivery rate in both normoxia and hyperoxia, but was independent of delivery rate in hypoxia. Mean O2 uptake in normoxia was 3.8 nmol O2 x cm-2 x min-1 at a delivery rate of 9.8 nmol.cm-2 x min-1 and 6.5 nmol O2 x cm-2 x min-1 at a delivery rate of 28.3 nmol.cm-2 x min-1. At any given bulk perfusion rate, oxygen uptake averaged about 49% lower in hypoxia than in normoxia, decreasing in proportion to the reduction of O2 tension difference between medium and blood. In hyperoxia, O2 uptake did not increase proportionally with the difference in O2 tension between blood and medium, averaging only 50% higher at a 2.4-fold greater O2 tension difference. Cutaneous diffusing capacity for O2 averaged 0.041 nmol O2 x cm-2 x torr-1 x min-1 during the first hour of perfusion in normoxia, and was not affected by reduction of ambient O2 tension. The results indicate that cutaneous O2 uptake in hypoxia is highly diffusion limited, and consequently, increases in cutaneous perfusion can not effectively compensate for reduction of ambient O2 tension. In hyperoxia, O2 uptake may be substantially perfusion limited because of reduced blood O2 capacitance at high O2 saturations.