A new model is presented for the study of the effects of supranormal temperatures on human tumors in vivo. Human tumors heterotransplanted serially in nude mice were heated in vivo by means of local radio-frequency heating. A lung carcinoma, a breast carcinoma, a colon carcinoma, and a malignant melanoma were studied. The tumors were transplanted s.c. in the inguinal area or under the kidney capsule of adult nude mice. The s.c. tumors were heated for 30 min. Temperatures of 43--44 degrees C were reached in the surrounding normal tissues, whereas in the center of the tumor temperatures of 46--49 degrees C were recorded. In 11 of 16 randomized pairs of mice, the growth of the tumor treated by hyperthermia was inhibited by 75% or more as compared with the growth of the untreated tumor control. No mortality and only temporary damage to skin and muscle were observed. The kidney tumors were also treated for 30 min, but it was possible to reach only 40 degrees C in the abdomen. Seventy-five % mortality was observed. Of seven randomized pairs evaluated, five exhibited a reduction of growth varying from 37 to 63%9 The model proposed appears to be a workable and promising one, especially for s.c. growing tumors.