The effect of daily hyperthermia on the murine normal and tumor tissues was investigated. Tumors were early generation isotransplants of a fibrosarcoma (FSa-II) and a mammary carcinoma (MCa) in C3Hf/Sed mice. Hyperthermia was given by immersing animal feet into a water bath at 45.5 degrees C. Tumor response was studied by TG time assay (determination of the time required for half of the treated animals' tumors to reach 1000 mm3 from the treatment day). Average peak foot reaction was also investigated to compare the therapeutic effectiveness of various fractionation regimens. In the first experiment the first dose (D1) of 10 min was followed by 10, 20, or 30 min daily doses. The treatment regimen "D1 of 10 min + daily 30 min" resulted in a significant therapeutic gain. The smaller doses were unable to overcome the repopulation of surviving tumor cells and the increasing magnitude of thermal resistance. To overcome tumor cell repopulation and thermal resistance, a regimen of increasing daily doses was attempted without success. These results indicated that doses following a D1 of 10 min must be as large as 30 min to obtain a therapeutic gain. Any fractionation regimens for MCa tumors, which developed the greatest thermal resistance among our animal tumors tested, failed to result in a therapeutic gain.