A series of experiments were designed to test the assumption that neuro-regulatory mechanisms associated with pituitary ACTH and melanotropin (MSH) secretions are interdependent. Stress elevates both ACTH and MSH activity in mouse pituitaries. There are nervous influences on the secretion of both of these hormones. We have undertaken to stimulate or block various components of the nervous control of these 2 hormones in order to determine whether the 2 are controlled by the same mechanisms or separate ones. We have exposed mice to neurotransmitter blocking agents against serotonin, norepinephrine and epinephrine – parachlorophenylalanine (PCPA), alpha-methyltyrosine (MT), propranolol – both with and without stress. Unilateral adrenalectomy with and without hydrocortisone replacement therapy were investigated. We found that none of the neuro-active substances altered stress elevation of ACTH and MSH. Unilaterally adrenalectomized stressed animals treated with hydrocortisone showed elevated pituitary MSH levels but non increased ACTH release, as measured by size of the remaining adrenal. Adrenalectomy of animals without replacement therapy showed both elevated pituitary MSH and increased ACTH activity Since the ACTH and MSH activity behave independently in the last described experiments, we conclude that ACTH and MSH are independently controlled.