The mouse neuroblastoma-rat glioma hybrid cell line NG108-15 was used to study the acute and chronic interaction of ethanol with intact neural cells. In the short term, ethanol inhibited opiate receptor binding, but after long-term exposure the cells exhibited an apparent adaptive increase in the number of opiate binding sites; this was reversible when ethanol was withdrawn. High concentrations of ethanol (200 mM) increased opiate binding after 18 to 24 hours, whereas lower concentrations (25 to 50 mM) produced similar changes after 2 weeks. This model system has potential for exploring the cellular and molecular mechanisms underlying ethanol intoxication, tolerance, and withdrawal.