Experiments were undertaken to examine the role of various endocrine factors (adrenal, pancreas, and testis) on daily (24h) variations in hepatic microsomal drug metabolism.Adrenalectomy and alloxan‐induced diabetes abolished the daily variation in drug metabolism as well as producing alterations in the basal levels of hepatic microsomal enzyme activity. Castration and insulin treatment abolished only the daily variation in ethylmorphine metabolism. These data suggest that various endocrine factors influence basal levels of hepatic drug metabolism; however, daily variations in hepatic drug metabolism are apparently not causally related to similar variations in plasma hormone levels.