The availability of human corticotropic hormone, together with sensitive methods of measuring ACTH and cortisol have recently made possible studies on the mode of secretion of these hormones, secreted episodically and parallel in man, and exogenous factors modulating their liberation. Time of day, meals, physical activity and stress, lack of sleep and REM sleep all have an influence on the daily rhythm of their secretion. Phenytoin, ketoconazole, and cyproterone acetat modify the secretion of cortisol; opiates and diazepam inhibit that of ACTH. The liberation of CRH and ACTH is stimulated by the appetite suppressant, serotonin, and inhibited by the appetite-stimulating antagonist cyproheptadine and by glucocorticoids.