The anticlastogenic effect of N-acetylcysteine was tested in vivo in mouse bone-marrow micronucleus assay. The frequencies of micronuclei induced by adriamycin (5 mg/kg i.p.) in bonemarrow cells were decreased by the oral administration of N-acetylcysteine at 12 h before adriamycin injection. The observed suppressing effect was not a reflection of a delay in the formation of micronuclei by the cytotoxic effect of N-acetylcysteine. The anticlastogenic effects of SH compound including N-acetylcysteine, cysteine, cystine, S-carboxy methylcysteine and glutathione were also investigated by the multiple pretreatment. Each SH compound was administered orally every day for 5 days and adriamycin (5 mg/kg i.p.) was injected at 24h after the last dose of test compound. N-acetylcysteine and glutathione showed significantly the suppressive effect at dose of 10 and 25 mg/kg for N-acetylcysteine and at the dose of 25 mg/kg for glutathione. Our study suggests that N-acetylcysteine is capable of protecting the chromosomal damages in the normal cells during cancer chemotherapy by adriamycin, and may act as an anticlastogen against induction of micronuclei by superoxide generating agent such as adriamycin.