The effect of acute nitroprusside-induced hypotension on plasma renin activity, catecholamine, and vasopressin concentrations was examined in eight chronically catheterized, conscious ewes. Nitroprusside was infused intravenously for one hour at rates adjusted to achieve a 20% decrease in mean blood pressure (dose range: 14–50 mg, or about 5.8–18.5 μg·kg-1·min-1). During hypotension, renin activity increased from 1.39 ± 0.49 to 3.92 ± 1.38 ng·ml-1.·h-1, catecholamine concentrations remained unchanged, and vasopressin increased from 1.7 ± 0.4 to 110 ± 52.7 pg/ml. A significant positive correlation was obtained between total nitroprusside dose and peak vasopressin level (r=0.749, P =0.015). No significant change in arterial-blood (PH, PO2, PCO2, plasma osmolality, or sodium concentration were observed throughout the experiment, thus eliminating the possibility of osmolar or hypoxic stimuli for the increased renin activity and vasopressin release. The magnitude of vasopressin release found in our studies implies that it plays a more important role than renin in defense against acute hypotension. In addition, the authors experiments suggest that variation in vasopressin release may be responsible for the variation of the dose of nitroprusside required to maintain hypotension.