The effect of adrenalectomy on renin secretion was investigated in conscious rats with glucocorticoid-induced hypertension. Adrenalectomized and sham-operated rats were made hypertensive with methylprednisolone acetate (20 mg/kg s.c. once/week X 2 weeks) supplemented with deoxycorticosterone pivalate (10 mg/kg s.c. once/week X 2 weeks). During the 2 week developmental phase of hypertension, tap water or isotonic saline was given as drinking fluid to respectively 10 and 13 adrenalectomized rats and 10 and 11 sham-operated rats. On the day of the acute administration of captopril or vehicle there was no significant difference in body weight, mean blood pressure, heart rate, serum electrolytes and plasma norepinephrine levels between the 4 groups of rats. Circulating epinephrine could not be detected in adrenalectomized rats. Plasma renin activity was markedly higher in adrenalectomized rats than in the sham-operated rats even after sodium supplementation. Captopril (10 mg/kg i.v.) produced no significant blood pressure lowering effect in rats given tap water to drink, either adrenalectomized (n = 11) or sham-operated (n = 10). These findings indicate that the activation of the renin-angiotensin system in adrenalectomized rats with glucocorticoid-induced hypertension is not directly mediated by the development of adrenal failure. They also show that the maintenance of high blood pressure in this form of experimental hypertension is not significantly enhanced when renin secretion is stimulated by adrenalectomy.