Cadmium has been known to induce the expression of the c-fos gene in various cell types including fibroblasts. To clarify the biological significance of c-fos induction by cadmium, mouse 3T3-like fibroblasts lacking c-fos were exposed to cadmium, and the resultant cellular damage was assayed by WST-8 (4-[3-(2-methoxy-4-nitrophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio] -1, 3-benzene disulfonate sodium salt) conversion, trypan blue exclusion, or lactate dehydrogenase leakage. The c-fos-deficient cells (f1 and f10) were affected more severely than the wild-type cells (NIH 3T3 and f20) with respect to both cell growth and cellular damage following exposure to 10 or 20 microM cadmium chloride. These results suggest that c-fos may play a protective role against the cytotoxic effects of cadmium at least in these 3T3-like fibroblasts.