Mutant cell lines, derived from the Chinese hamster V79 cell line, deficient in poly(adenosine diphosphate-ribose) polymerase activity, and previously shown to be resistant to topoisomerase II inhibitors, were found to be hypersensitive to camptothecin, a topoisomerase I inhibitor. In all the cell lines, camptothecin induced dose-dependent protein-associated DNA single-strand breaks and sister chromatid exchanges. The increased sensitivity to camptothecin-induced cytotoxicity was not associated with an increase in DNA single strand breaks or sister chromatid exchanges. These results suggest the absence of any direct causal relation between (1) camptothecin induced sister chromatid exchanges and cytotoxicity or (2) camptothecin induced DNA strand breaks and cytotoxicity. The hypersensitivity of these mutant cell lines to camptothecin suggests that poly(adenosine diphosphate-ribose) polymerase is involved with topoisomerase I in modulating camptothecin induced cytotoxicity.