The central cardiovascular responses induced by neuropeptide Y (0.25 nmol) and adrenaline (2.00 nmol) given i.c.v. in close to maximal doses in the awake, unrestrained male rat were studied following changes in the pituitary-adrenal activity. Adrenalectomy (1 week) alone significantly reduced the vasodepressor response to i.c.v. adrenaline but not to i.c.v. neuropeptide Y. Corticosterone replacement treatment (5 mg kg-1 x 2, i.p., 1 week) significantly reduced both the maximal (peak) and overall (area) vasodepressor responses to i.c.v. adrenaline and neuropeptide Y (only overall responses) in the adrenalectomized rat. Corticosterone treatment alone in the sham-operated rat highly significantly reduced the vasodepressor responses to both i.c.v. adrenaline and neuropeptide Y. The bradycardic action of centrally administered neuropeptide Y was no longer significant after alterations in pituitary-adrenal activity. The present results suggest that corticosterone treatment can abolish the centrally evoked vasodepressor responses to close to maximal doses of adrenaline and neuropeptide Y, which may contribute to their hypertensive properties in man. Finally, after adrenalectomy the central vasodepressor responses to neuropeptide Y dominate, since the adrenergic vasodepressor responses are selectively reduced. This dominance is reduced by corticosterone replacement treatment. The results indicate an antagonistic role of adrenocortical steroids in control of centrally induced acute vasodepressor responses to neuropeptide Y and adrenaline.