The heavy metal cadmium is a carcinogen in long-term rodent studies and is a suspect human carcinogen. Cadmium scores negative in the Ames Salmonella mutagenicity assay and in most other short-term genotoxicity assays, but induces deletions in the yeast Saccharomyces cerevisiae. We have investigated whether cadmium induces an oxidative stress in S. cerevisiae which may be responsible for its recombinagenic activity. The free radical scavenger N-acetylcysteine blocked toxicity and recombination induced in S. cerevisiae by cadmium. Yeast strains deficient in the antioxidant defense enzymes superoxide dismutase or gamma-glutamylcysteine synthetase were hypersensitive to cadmium toxicity. Cells grown in the absence of oxygen were more resistant to cadmium. An intracellular free radical-sensitive reporter compound was activated in S. cerevisiae exposed to cadmium. Toxicity or recombination induced by the mutagenic carcinogen methyl methanesulfonate were unaffected in any of the above experiments. These results suggest that the toxicity and recombinagenic activity of cadmium in S. cerevisiae is caused by oxidative stress.