In a previous study we reported the presence of specific nonopiate beta-endorphin (BE) binding sites in peripheral tissues of the rat (Dave JR, Rubinstein N, Eskay RL: Evidence that beta-endorphin binds to specific receptors in rat peripheral tissue and stimulates the adenylate cyclase-adenosine 3',5'-monophosphate system. Endocrinology 117:1389-1396, 1985). The objective of this study was to determine the effect of chronic ethanol administration in vivo on specific nonopiate binding of BE in hepatic and kidney membranes. Experimental animals were exposed continuously for 14 days to ethanol vapor in an inhalation chamber at vapor levels sufficient to maintain blood ethanol levels greater than 120 mg/100 ml, whereas control animals were maintained in ethanol-free chambers. Chronic ethanol treatment decreased [125I]BE binding to hepatic and kidney membranes by approximately 35%, which was due to a decrease in the number of BE binding sites. Chronic ethanol treatment decreased immunoreactive BE in plasma by greater than 80%. In vitro exposure of hepatic and kidney membranes from control animals to ethanol resulted in a dose-related enhancement of BE binding with maximal enhancement of 50-65% being observed at 0.2% ethanol concentration. In contrast, the addition of ethanol in vitro to hepatic and kidney membranes derived from rats chronically exposed to ethanol in vivo did not affect BE binding. Our findings demonstrate that chronic alcohol exposure lowers immunoreactive BE in plasma and reduces BE binding in hepatic and kidney membranes. The observed reduction of BE binding may be due to ethanol-induced changes in membrane composition.