The interaction between hyperthermia and a DNA topoisomerase I inhibitor, 7-ethyl-10-(4-(1-piperidyl)-1-piperidyl)-carbonyloxy- camptothecin (CPT-11), was studied in the mouse mammary carcinoma FM3A cells. When the cells were treated with CPT-11 at a concentration of 5 micrograms/ml and 44 degrees C hyperthermia for 60 min, an enhancement of formation of single stand breaks (ssb) of DNA was observed. However, a decrease of ssb was observed when hyperthermia was combined with CPT-11 at 50 micrograms/ml. For inhibition of DNA synthesis additive effects were observed for treatment with CPT-11 at 5 micrograms/ml combined with hyperthermia. On the other hand, protective effects were observed for the combined treatment at 50 micrograms/ml. These results indicate that the hyperthermic modification of the effect of CPT-11 on the induction of DNA damage was diverse at low or high concentrations.