The effects of the genotype of alcohol dehydrogenase-2 (ADH2) and mitochondrial aldehyde dehydrogenase (ALDH2) on drinking behavior were investigated in a population of 451 Japanese. Although the ALDH2*2 allele had a significant inhibitory effect on alcohol consumption, hence on drinking problems, the apparent association was not confirmed between ADH2 genotype and overall drinking patterns for either males or females. However, the frequency of the ADH2*2 allele was significantly lower in male Japanese classified as alcoholic on the basis of the Kurihama Alcoholism Screening Test than in nonalcoholic males. These results corroborate a previous study that revealed a significantly lower ADH2*2 allele frequency in hospitalized Japanese alcoholics than in the general population. Together, these studies suggest that the ALDH2*2 allele has an inhibitory effect on drinking behavior, irrespective of the level of alcohol consumption, whereas the effect of the ADH2 polymorphism only becomes apparent in individuals with higher alcohol consumption, such as alcoholics.