The effects of intraperitoneal administration of ethanol, 0.5, 1.0, and 2.0 g/kg body weight, on the extracellular concentrations of dopamine (DA), serotonin (5-HT), and their major metabolites were studied in the nucleus accumbens (ACC) of alcohol-naive, selectively bred high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) lines of rats using the technique of microdialysis. In both lines, the extracellular levels of DA were increased following the injection of 1.0 and 2.0 g of ethanol/kg body weight while only the 2.0-g/kg dose elevated the concentration of 5-HT. None of the ethanol doses altered the extracellular levels of the major metabolites of DA and 5-HT. Dose-response curves for DA and 5-HT release indicated no marked difference in the sensitivity to ethanol between the lines. Local perfusion with 60 mM K+ through the microdialysis probe markedly enhanced the release of DA and 5-HT in the ACC of both lines; there was a small difference between the lines in the amounts of DA, but not 5-HT, released by K+-stimulation. Overall, the results indicate that (1) the ACC DA system is more sensitive than the ACC 5-HT system to intraperitoneal ethanol administration in both lines and (2) there is no evidence for a relationship between alcohol preference and sensitivity of the ACC DA and 5-HT systems to acute intraperitoneal ethanol administration.