Indium-111-bleomycin complex (111In-BLMC) is a radiopharmaceutical agent that produces tumor regression in mouse glioma in vivo and kills human small cell lung cancer (SCLC) cells in vitro. The interaction between hyperthermia and 111In-BLMC against human SCLC (N417) cells was studied for bleomycin (BLM) (15 micrograms/ml) or 111In-BLMC (40-50 microCi carried by 15 micrograms BLM/ml) for 5 min or 1.5, 2, or 4 hr at 37 degrees C or 43 degrees C exposures. Cell survival was determined by colony formation in soft agarose. There was a synergistic effect for 111In-BLMC and hyperthermia for cell killing. At 37 degrees C, the percent survival of N417 cells for BLM alone was 25.9%, and for 111In-BLMC it was 13.2%; at 43 degrees C, survival was 5.3% for BLM alone and 1.2% for 111In-BLMC by a 4 hr treatment. Effectiveness was greater when 111In-BLMC was combined with hyperthermia.