Suppression of the adrenergic system by injection of reserpine (0.2 mg/kg for 2 days) into male rats resulted in a decrease of the pituitary MSH content. The same effect was observed 30, 60, or 120 min after intraperitoneal administration of dibenamine (30 mg/kg), while propranolol (6 mg/kg), a 6 beta-adrenergic blocking agent, produced no change. Pretreatment of the animals with reserpine or with dibenamine prevented the drop in pituitary MSH content that follows intravenous injection of 2 ml of a 2% solution of sodium chloride, but not that observed after administration of MSH-releasing factor. Depletion of pituitary MSH content induced by injection of hypertonic saline or of MSH-releasing factor could be blocked by implants of norepinephrine or dopamine placed in the 3rd ventricle, but not by those placed in the lateral ventricle or the pituitary gland. Implants of carbachol were without effect. At 30 min after implantation of norepinephrine into the 3rd ventricle, a depletion of the hypothalamic content of MSH-release-inhibiting factor was observed. It is concluded that the hypothalamic neurons that secrete this inhibiting factor are under the tonic influence of catecholaminergic fibers. Blockade of this influence results in the release of MSH. An alpha-adrenergic receptor seems to be involved in this action.