In order to examine whether ethanol treatment has selective or differential effects on brain binding sites for opiates, male Sprague Dawley rats were fed for 15 or 21 days with a complete liquid diet containing 6.5% ethanol (v:v) or an isocaloric amount of sucrose. The binding of 3H-DADL-enkephalin, 3H-dihydromorphine and 3H-naloxone to the brain membranes from rats treated with ethanol was increased. However, addition of ethanol directly in the incubation medium decreased the binding of 3H-DADL enkephalin and increased the binding of 3H-dihydromorphine to brain membranes from both control and ethanol treated rats. Direct exposure of brain membranes to ethanol caused no significant change in the binding of 3H-naloxone. Thus chronic ethanol ingestion alters the binding of opiate ligands to brain membranes. Furthermore, the direct effect of ethanol appears to be different for the different classes of opiate binding sites.