To examine the association between alcohol consumption and mortality in Japan, where mortality and lifestyle differ substantially from Western countries, a population-based prospective study was conducted in four public health center areas as part of the Japan Public Health Center-based prospective study on cancer and cardiovascular disease (JPHC). After excluding subjects with self-reported serious diseases at baseline, 19,231 men aged 40-59 years who reported their alcohol intake were followed from 1990 through 1996, and 548 deaths were documented. The association between all-cause mortality and alcohol consumption was J-shaped. The lowest risk was observed for men who consumed 1-149 g/week (relative risk (RR) = 0.64, 95% confidence interval (CI) 0.46, 0.88), while the highest risk was seen for men who consumed > or =450 g/week (RR = 1.32, 95% CI 1.00, 1.74), after adjustment for possible confounders. The association did not change after excluding deaths that occurred in the first 2 years of follow-up. However, the association was modified by smoking, and beneficial effects of moderate drinking were largely limited to nonsmokers. The risk of cancer death showed a similar trend, but increased more in heavy drinkers. The background characteristics of moderate drinkers were healthier than either nondrinkers or heavy drinkers. The authors conclude that moderate alcohol consumption was associated with the lowest risks of all-cause and cancer mortality, especially among nonsmokers.