Ethanol (EtOH) in the presence of the EtOH-metabolizing enzyme, alcohol dehydrogenase (ADH) leads to the induction of sister-chromatid exchanges (SCEs) in human peripheral lymphocytes in vitro. Acetaldehyde (AA) induces SCEs, whose frequencies are lowered in the presence of the AA-metabolizing enzyme, aldehyde dehydrogenase (ALDH). EtOH in the presence of ADH produces more SCEs than EtOH in the presence of ADH and ALDH. These data are interpreted to show that not ethanol itself, but its first metabolite acetaldehyde is mutagenic.