Daily i.p. injection of reserpine for 9 days strongly depletes hypothalamic norepinephrine (NE); after an initial activation, adrenocortical function returns to control values by the 5th day. Tyrosine hydroxylase (TH) activity in the brain stem of reserpine-treated rats exhibits a progressive increase. Alpha-methyl-para-tyrosine (α-MpT) in rats chronically pretreated with reserpine provokes adrenocortical activation and a further decrease of hypothalamic NE. Exogenous ACTH in the same animals revealed an unimpaired adrenocortical reactivity after prolonged treatment with reserpine. These results seem to suggest that the disappearance of adrenocortical activation following long-term treatment with reserpine is due to the stimulated formation of a small functional pool of NE available for the tonic inhibition of CRF-ACTH secretion.