Verapamil has previously been shown to have enhanced the cytotoxicity of VP-16-213 against malign cell lines in vitro. In this study the cytotoxic effects of verapamil on the cytotoxicity of etoposide against transformed mouse fibroblasts (L-strain cell) were examined. When verapamil was used alone, after 8 hrs, DNA synthesis was increased with respect to the control cells (p<0.01) and the initial increase of DNA synthesis was higher with the lowest concentration of verapamil (2 mu g/ml) (p<0.01). In cells that were treated with verapamil and etoposide, after 16 hrs, etoposide cytotoxicity was enhanced and the DNA synthesis decreased (p<0.01). This enhancement augmented with the increasing doses of verapamil (p<0.01). Although the initial stimulatory effect of verapamil on the DNA synthesis may have some role in the enhancement of etoposide cytotoxicity, the involvement of some other mechanisms is postulated.