The effects of chronic glucocorticoid treatment on sympathoadrenomedullary function were assessed in conscious unrestrained Wistar-Kyoto rats. Cortisol (25 mg/kg.day), administered for 7 days using a sc reservoir pump, suppressed activity of the hypothalamo-pituitary-adrenocortical axis, as indicated by markedly decreased levels of corticotropin (ACTH) and corticosterone and decreased adrenal weight. Cortisol also decreased body weight and increased blood pressure to hypertensive levels without affecting plasma sodium or potassium. Basal levels of plasma epinephrine were markedly decreased, indicating suppression of adrenomedullary secretion. Plasma norepinephrine levels also were decreased, but to a smaller extent than epinephrine, and levels of dihydroxyphenylglycol, an intraneuronal metabolite of norepinephrine, were unaffected. Plasma catecholamine responses to nitroprusside-induced hypotension were not altered by cortisol. The results suggest that chronic cortisol treatment suppresses basal hypothalamo-pituitary-adrenocortical and basal adrenomedullary activity in conscious unrestrained rats without impairing reflexive activation of the sympathoadrenomedullary system.