The effect of ethanol on glucose utilization during hyperinsulinemia was studied by the euglycemic clamp technique. Normal subjects were given 1 g ethanol/kg body weight for 210 min (oral priming dose of 0.67 g/kg followed by iv infusion of 0.33 g/kg) or 0.9% saline. Insulin infusion, started 90 min after the beginning of ethanol administration, resulted in a mean plasma insulin concentration of 87 +/- 5 (SEM) mU/liter. Plasma glucose was maintained at 5.2 mmol/liter. The rate of glucose metabolism was 23% lower during ethanol (7.1 +/- 0.1 mg/kg X min) than during the control (9.0 +/- 0.8 mg/kg X min) experiment (P less than 0.001). During hyperinsulinemia blood lactate concentrations rose in the control study but this change was abolished by ethanol. The insulin-induced fall of serum triglyceride levels was also inhibited by ethanol. It is concluded that acute intake of alcohol in moderate doses induces insulin resistance.