The sensitivity of cells exposed in vitro to the antibiotics bleomycin or adriamycin is only mildly increased at 41° over that seen at 37°. However, at 430 a marked synergism between the effects of hyperthermia and drug is observed. This synergism can also be demonstrated to occur in solid tumors in vivo. Cells after bleo mycin exposure at 370 repair potentially lethal damage, and 430 inhibits this repair. This inhibition may in part account also for the observed sensitization of the cells to bleomycin, but not to adriamycin, since for the latter no repair can be demonstrated. However, fluorescence measurements show that at 430 much more adriamycin is able to enter the cells than at 37°. The possible implications of the results for cancer treatment are discussed. Bleomycin (1) and adriamycin (2) are two antibiotics currently used in cancer chemotherapy. Both agents show some degree of effectiveness against a variety of solid tumors. However, as with all other currently used anti-tumor drugs, normal tissue toxicity limits dosages to levels far below those required to sterilize most malignant lesions. Attempts to improve the efficacy of treatment by simultaneously or sequentially administering several drugs (with differing modes of cytotoxic action and nonoverlapping normal tissue toxicities) have been only moderately successful. Hence, any treatment or combination of treatments that would increase tumor cell toxicity without a concomitant increase in damage to the treatment-limiting normal tissue would be highly desirable. In this preliminary communication, we show that above 420 the cell-killing ability of these two antibiotics is markedly increased when compared to 370 and that this difference holds both in vitro and in a solid tumor system in vivo. Local heating of tumor volumes to 430 appears technically feasible. Since treatment-limiting tissue appears to be lung for bleomycin (3) and heart for adriamycin (4), the data presented here may point the way towards greatly improved chemotherapeutic management of isolated lesions not located near those