To investigate whether sensitivity to the induction of micronuclei by acetaldehyde is associated with genetic polymorphisms of the aldehyde dehydrogenase-2 (ALDH2) gene, cytokinesis-block micronucleus (CBMN) assays were performed on peripheral lymphocytes from 47 healthy human subjects exposed to acetaldehyde in vitro. Facial flushing following alcohol intake was analyzed to determine if it was correlated with ALDH2 gene polymorphisms. The frequencies of the ALDH2 genotypes ALDH2(1)/ALDH2(1), ALDH2(1)/ALDH2(2), and ALDH2(2)/ALDH2(2) were 66.0, 27.7, and 6.4%, respectively, in the 47 subjects. Therefore, 34% of the studied subjects carried the mutant allele ALDH2(2), which is associated with the lack of enzyme activity. The frequency of micronuclei induced by acetaldehyde increased in a dose-dependent manner with the largest increase seen in subjects that were homozygous for the ALDH2(2) allele. A significant association was observed between the ALDH2 genotype and alcohol-induced facial flushing. Average alcohol consumption of the study subjects was also associated with the ALDH2 genotype. The frequency of heavy drinking was significantly higher among subjects with the ALDH2(1)/ALDH2(1) genotype than among subjects with the ALDH2(2) allele (ALDH2(1)/ALDH2(2) and ALDH2(2)/ALDH2(2) genotypes). Alcohol-induced facial flushing was also associated with an increased frequency of micronuclei in lymphocytes treated with acetaldehyde. The results suggest that the ALDH2 genotype is significantly associated with acetaldehyde-induced micronuclei and alcohol-induced facial flushing.