Previous studies of the relationship between the endogenous opioid system and alcohol consumption have reported contradictory results. To shed light on this connection, we compared plasma concentrations of β-endorphin, adrenocorticotropic hormone, and cortisol in 70 alcoholic persons after different periods of abstinence and a group of 80 control subjects. Plasma β-endorphin was decreased in alcoholics (18.61 ± 1.38 vs. 39.31 ± 3.44 pg/ml), even after more than 10 years' abstinence. This effect may be mediated by the tetrahydroisoquinoline system, and may thus result from chronic alcohol consumption. On the other hand, lowered circulating concentrations of β-endorphin may be a cause, rather than an effect, of alcoholism. Plasma levels of adrenocorticotropic hormone and cortisol did not differ in alcoholics and controls (19.29 ± 1.66 vs. 13.27 ± 1.85 pg/ml for ACTH, 20.37 ± 0.78 vs. 17.22 ± 0.64 ng/ml for cortisol), and thus appear to have no relation with chronic alcohol consumption.