The role of circulating epinephrine in the regulation of renin release was studied in unanesthetized rats with glucocorticoid-induced hypertension. Biadrenalectomized Wistar rats were made hypertensive with methylprednisolone (20 mg/kg s.c. weekly) for 2 weeks and supplemented with deoxycorticosterone pivalate (10 mg/kg s.c. weekly). Sham-operated controls received the same treatment. Baseline weight, mean intra-arterial blood pressure and heart rate of the groups were the same. In both adrenalectomized and sham-operated rats plasma renin activity was determined after a 30 min infusion of the beta-adrenoceptor stimulant isoproterenol (40 ng/min) or its vehicle. Isoproterenol had no blood pressure effect and accelerated heart rate to a similar extent in rats with and without adrenals. Plasma renin activity was significantly higher in epinephrine-deficient than in sham-operated rats. Renin secretion was significantly enhanced by isoproterenol in both groups of rats. These data therefore indicate that in rats with glucocorticoid-induced hypertension the renin-angiotensin system is activated by adrenalectomy, despite the fact that adrenal insufficiency cannot develop. It also appears that rats lacking of circulating epinephrine for a prolonged period do not exhibit an abnormal responsiveness of renin secretion to the stimulation of renal beta-adrenoceptors.