The interaction of ethanol with the nervous system produces acute intoxication, tolerance and withdrawal phenomena. Additionally, there are several alcohol-related neurological disorders which develop in alcoholic patients. Current evidence suggests that ethanol produces some of these changes by altering the structure and function of neural membranes. Therefore, neurotransmitter receptors and receptor-dependent molecular events in the nervous system may be highly sensitive to ethanol. The murine neuroblastoma X glioma hybrid cell line NG108-15 was used to study the acute and chronic interactions of ethanol with intact cells. Ethanol acutely inhibited opiate receptor binding, but after chronic exposure the cells exhibited an apparent adaptive increase in the number of opiate binding sites; this was reversible when ethanol was withdrawn. High levels of ethanol (200 mM) increased opiate binding after 18-24 hours; lower concentrations (25-50 mM) produced similar changes after two weeks. This model system has great potential for exploring the cellular and molecular mechanisms which underlie ethanol intoxication, tolerance and withdrawal.