Hypotension stimulates the secretion of adrenocorticotropin (ACTH) and vasopressin (AVP) and increases plasma levels of angiotensin II (ANG II). Because AVP and ANG II increase ACTH secretion, the present experiments were performed to evaluate the role of these peptides in the increases in plasma ACTH and glucocorticoid concentrations produced by hypotension in conscious dogs. This was accomplished by determining whether administration of receptor antagonists to vasopressin, [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine]Arg8-vasopressin, and ANG II (saralasin), reduced the ACTH and glucocorticoid responses to infusion of four doses of the vasodilator nitroprusside. Nitroprusside (NP) infusion produced dose-dependent decreases in mean arterial pressure. Larger decreases in arterial pressure were produced in dogs pretreated with the AVP antagonist or with both saralasin and the vasopressin antagonist. Left and right atrial pressures also fell with NP infusion, and larger decreases in atrial pressures were found in dogs pretreated with the AVP antagonist. Finally, NP infusion increased plasma glucocorticoid concentration and plasma ACTH concentration. Both the glucocorticoid and the ACTH responses to hypotension were reduced in dogs given the AVP antagonist and in dogs given both saralasin and the AVP antagonist, but there was no difference in the effect of AVP blockade alone vs. the effect of combined AVP and ANG II blockade. These data suggest that AVP, but not ANG II, is required for normal glucocorticoid and ACTH responses to hypotension. They also suggest that AVP is necessary for normal maintenance of arterial blood pressure and atrial pressures during NP infusion.