Feeding behavior elicited by injection of norepinephrine (NE) into the paraventricular nucleus (PVN) of satiated rats has been shown to be abolished by hypophysectomy. To determine the specific nature of this dependence of NE's action on pituitary hormones, the efficacy of PVN-injected NE was examined in rats subjected to hypophysectomy, as well as to adrenalectomy, thyroidectomy, and gonadectomy, and also in operated rats receiving hormone replacement therapy. The feeding response induced by NE was almost completely abolished in adrenalectomized as well as hypophysectomized animals, but remained unimpaired after thyroidectomy and gonadectomy. The NE response was significantly restored in hypophysectomized rats by daily subcutaneous injections of corticosterone, but not by thyroxine, testosterone, insulin, or the mineralocorticoid deoxycorticosterone. In adrenalectomized rats, subcutaneous corticosterone implants as well as daily corticosterone injections (as opposed to deoxycorticosterone injections) effectively restored the NE eating effect. Radioimmunoassay of plasma corticosterone indicated that the level of hormone was positively correlated with the strength of the animals' response to the NE injection. These findings demonstrate that the loss of response to NE subsequent to hypophysectomy is due to a disruption of the hypothalamo-pituitary-adrenal axis. The glucocorticoids of the adrenal gland appear to be the essential humoral factor interacting permissively with PVN-injected NE to elicit feeding.