Vasopressin and angiotensin II markedly stimulated oxygen uptake in the perfused rat hindlimb. The increase due to each agent approached 70% of the basal rate, and was greater than that produced by a maximal concentration of norepinephrine. Half-maximal stimulation occurred at 60 pM vasopressin, 0.5 nM angiotensin II and 10 nM norepinephrine. Angiotensins I and III were less potent than angiotensin II. For each agent, the dose-dependent increase in oxygen uptake coincided with a dose-dependent increase in perfusion pressure. The effects of both vasopressin and angiotensin to increase oxygen uptake and pressure were not inhibited by either phentolamine, propranolol or a combination of the two, but were completely inhibited by the vasodilator, nitroprusside. Nitroprusside also inhibited flow-induced increases in hindlimb oxygen uptake and perfusion pressure. The findings indicate a key role for the vascular system in the control of hindlimb oxygen uptake.