Alcohol dehydrogenase (ADH) polymorphisms were evaluated among 95 Native American Mission Indians. Approximately equal frequencies of ADH3*1 and ADH3*2 alleles were found. Twelve individuals were heterozygous for ADH2*3, an allele previously identified only in persons of African origin. None of the individuals with ADH2*3 alleles was of purely Native American descent, although none had known African ancestry. These results suggest that these candidate genes deserve broader study among Native Americans and may provide increased understanding of the likely polygenic contributions to alcohol-related disorders in this population.