Glucocorticoids inhibit the plasma vasopressin responses to hemorrhage and hypoxia in dogs. Attempts to demonstrate glucocorticoid inhibition of vasopressin secretion in fetal sheep have been unsuccessful, suggesting the possibility that there is an influence of development on the expression of this interaction, or that the interaction cannot be demonstrated in all mammalian species. This study was designed to investigate these two possibilities. Adult ewes chronically prepared with carotid arterial loops, were subjected to 5 hr infusions of cortisol at a rate of 6 ug/kg min or vehicle (5% ethanol in saline). The infusion of cortisol increased plasma cortisol concentration from 26 +/- 3 to 46 +/- 8 ng/ml, while vehicle infusion was associated with a decrease in plasma cortisol concentration from 23 +/- 4 to 15 +/- 3 ng/ml. One hr after the end of the cortisol or vehicle infusions, vasopressin secretion was stimulated by arterial hypotension produced by 10 min infusions of sodium nitroprusside (20 ug/kg min). Nitroprusside decreased arterial blood pressure equally in both groups. Plasma vasopressin concentrations were increased to peak concentrations of 92 +/- 33 and 116 +/- 20 pg/ml in the vehicle- and cortisol-infused groups, responses which were not significantly different as tested by ANOVA. We conclude that increases in plasma cortisol concentration, equal to those observed during responses to stressors, do not inhibit vasopressin secretion in this species.