Evidence regarding the association between alcohol consumption and type 2 diabetes risk remains inconsistent, particularly with regard to male-female differences. The authors conducted a prospective study of type 2 diabetes risk associated with alcohol consumption in a cohort of 12,261 middle-aged participants of the Atherosclerosis Risk in Communities Study (1990-1998), who were followed between 3 and 6 years. Alcohol consumption at baseline was characterized into lifetime abstainers, former drinkers, and current drinkers of various levels. Incident diabetes was determined by blood glucose measurements and self-report. After adjustment for potential confounders, an increased risk of diabetes was found in men who drank >21 drinks/week when compared with men who drank < or =1 drink/week (odds ratio = 1.50, 95% confidence interval: 1.02, 2.20) while no significant association was found in women. This increased diabetes risk among men who drank >21 drinks/week was predominantly related to spirits rather than to beer or wine consumption. The relative odds of incident diabetes in a comparison of men who drank >14 drinks of spirits per week with men who were current drinkers but reported no regular use of spirits, beer, or wine were 1.82 (95% confidence interval: 1.14, 2.92). Results of this study support the hypothesis that high alcohol intake increases diabetes risk among middle-aged men. However, more moderate levels of alcohol consumption do not increase risk of type 2 diabetes in either middle-aged men or women.