Several observational and epidemiologic analyses suggest that moderate drinking of alcohol (usually two drinks per day) may have beneficial effects on the heart. Specifically it may reduce the incidence of ischemic heart disease and improve the outcome after a myocardial infarction. The purpose of this study was to test the hypothesis that long-term, moderate consumption of alcohol has a direct cardioprotective effect, reducing myocardial infarct size in rats subjected to ischemia/reperfusion. Two groups of rats were given alcohol in their drinking water at concentrations of 15% or 36%; control rats received water (n = 10 for all groups). After 16 weeks of treatment, the rats were anesthetized and subjected to 60 min of coronary artery occlusion and reperfusion. The ischemic risk region (% LV) was not significantly different among groups. Infarct size (% risk zone) was 49+/-7%, 44+/-4%, and 50+/-8%, respectively (p = 0.79). Thus no significant differences in infarct size between control and alcohol-fed rats were observed. There was no correlation between alcohol level and infarct size in alcohol-treated rats (r = 0.20, p = 0.45). Arterial pressures were lower in the 36% group at baseline and throughout the study compared with the control and 15% groups, but heart rates were similar in all groups. Moderate consumption of alcohol failed to alter infarct size compared with control and thus it is unlikely that alcohol drinking has a direct myocardial-protecting effect on the outcome of ischemia and reperfusion.