OBJECTIVE To test the hypothesis that insulin-mediated glucose uptake is enhanced in light-to-moderate alcohol consumption. METHODS This is a case-control study of healthy volunteers, divided into nondrinkers and light-to-moderate drinkers based on their history of alcohol consumption. The study was performed at the General Clinical Research Center at Stanford University Medical Center and involved 40 volunteers, 20 men and 20 women. Measurements were made of the plasma glucose and insulin responses to an oral glucose challenge, fasting plasma lipid and lipoprotein concentrations, and steady-state plasma insulin (SSPI) and steady-state plasma glucose (SSPG) concentrations in response to a continuous infusion of somatostatin, insulin, and glucose. RESULTS Light-to-moderate drinkers (10-30 g/day) had lower integrated plasma glucose (17.8 +/- 0.8 vs. 19.8 +/- 0.9 mM/h, P < 0.02) and insulin (600 +/- 65 vs. 1,075 +/- 160 pM/h, P < 0.01) responses to the glucose challenge and higher fasting plasma high-density lipoprotein (HDL) cholesterol concentrations (1.46 +/- 0.08 vs. 1.25 +/- 0.08, P < 0.02). Despite similar SSPI concentrations of approximately 300 pM, SSPG concentrations were lower (P < 0.01) in light-to-moderate drinkers (6.7 +/- 0.8 vs. 10.7 +/- 1.2 mM). Results were independent of age, body mass index, ratio of waist-to-hip girth, and estimates of level of habitual physical activity. CONCLUSIONS Light-to-moderate alcohol consumption in healthy men and women is associated with enhanced insulin-mediated glucose uptake, lower plasma glucose and insulin concentrations in response to oral glucose, and a higher HDL-cholesterol concentration. The changes in glucose and insulin metabolism may contribute to the lower risk of coronary heart disease described in light-to-moderate drinkers.