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The half-life of plasma cortisol in the rhesus monkey (M. mulatta), determined by two methods, was about 130 min and longer than that in man; it was unaffected by administration of dexamethasone. Dexamethasone (5 mg, i.v.) immediately inhibited the secretion of ACTH from the monkey pituitary. The plasma half-life of NH₂-terminal immunoreactive ACTH was found to be about 55 min which was much longer than the biological half-life. The adrenal synthesis of cortisol was inhibited by metyrapone which caused a prompt increase in the plasma concentration of ACTH and 11-deoxycortisol. The hypothalamicpituitary-adrenal system of the rhesus monkey sedated with phencyclidine hydrochloride responded rapidly to alteration in the level of steroids in the circulation.