Acetaldehyde, the first metabolite of ethanol oxidation, in concentrations ranging from 100 microM to 400 microM caused a dose-dependent linear increase in the frequency of sister-chromatid exchanges (SCE) in cultured human peripheral lymphocytes. The SCE frequency was on an average 2-fold higher when the cells were exposed to the acetaldehyde after 24 h incubation instead of at the time of mitogen stimulation (0 h). When acetaldehyde was added together with the potent aldehyde dehydrogenase inhibitor 1-aminocyclopropanol (0.1 mM), the SCE response was significantly (p less than 0.05) increased. The present results indicate that acetaldehyde is metabolized within human lymphocytes, and, moreover, that alcohol consumption during treatment with drugs that inactivate aldehyde dehydrogenase may cause a further increased incidence of acetaldehyde-induced SCE and concomitant lesions.