To elucidate the effect of ethanol on the secretion of ACTH and beta-endorphin (BE) as the representatives of the pro-opiomelanocortin (POMC) system, as well as cortisol as the hypophyseally regulated peripheral hormone, we measured concentrations of serum ethanol and plasma ACTH, BE, and cortisol at 1- to 4-hr intervals for 12 hr after administration of 0.5 and 1.0 g ethanol/kg of body weight and placebo drinks between 1900-1945 hr to nine healthy volunteers according to a double-blind, cross-over design. Plasma ACTH, BE, and cortisol showed an expected diurnal rhythm with the highest levels at 0700 hr. Intake of ethanol had no statistically significant effects on plasma ACTH up to 0700 hr in the morning. The higher dose caused increased levels of BE at 0100 hr and both doses at 0200 hr. Plasma cortisol at 0400 hr was higher in subjects receiving 1.0 g ethanol/kg than in those receiving placebo (p