The histopathological effects of hyperthermia with or without radiation were investigated in a transplanted mouse mammary carcinoma. Since the histopathological changes following hyperthermia differed greatly between the center and periphery of a tumor, we analyzed the changes in each area separately according to a semi-quantitative method developed by us. Three days after hyperthermia at 44 degrees for 45 min, undamaged tumor cells were found mostly in the tumor periphery adjacent to normal tissues. This phenomenon was observed when the entire tumor could be heated almost homogeneously. When a tumor was treated by heat alone, the thermal damage disappeared 7 days after treatment. On the other hand, treatment with hyperthermia plus radiation caused pronounced damage in the tumor center and tumor periphery 7 and 14 days after treatment. These combination effects depended on the radiation dose. The present findings demonstrate that combination of high doses of irradiation and hyperthermia is very effective for potentiating the thermal damage in the tumor periphery.