The demonstration of the existence of a gonadotrophin-inhibiting factor (Landau, Schwartz & Soffer, 1960) poses the question of whether or not a comparable inhibitor exists for other trophic hormones of the hypophysis. The following experiment was devised under a double supposition: (1) that the trophic hormone and 'inhibitor' co-exist in a normal organism, and (2) that the 'inhibitor' is produced in the periphery (not in the hypophysis). In such a case, the removal of the hormone and its source, should leave in the circulation a substance capable of inhibiting the action of an exogenous hormone. The purpose of this communication is to report findings which suggest the existence of a substance inhibiting adrenocorticotrophic hormone (ACTH) in the plasma of hypophysectomized rats. Male rats of the Sprague—Dawley strain were used. ACTH activity was demonstrated by the depletion of adrenal ascorbic acid in hypophysectomized rats, as described by Sayers (1957). Three groups