Biochemical and clinical studies have revealed a profound and selective toxic effect of elevated temperatures on tumor cells. Whereas the oxygen uptake of Novikoff hepatoma and Ehrlich ascites carcinoma cells was considerably less at 427deg;C than at 38°C, there was little difference in respiration at these two temperatures in normal and regenerating liver. The inhibition of the respiration of Novikoff hepatoma cells was irreversible after 90 min. There was no significant effect of temperature on anaerobic glycolysis. In 22 patients with cancers of the limbs the temperature in the tumors was raised to 41.5° to 43.5°C for several hours in 25 regional perfusions with prewarmed blood. Severe complications in some patients lead to six deaths and three immediate amputations. Intensive post‐treatment care was required. Three patients failed to respond; four could not be evaluated and all others had regressions. Grossly the tumors disappeared totally in ten patients, of which three recurred. Histological evaluation of multiple biopsies demonstrated complete massive necrosis in eight cases, of which none recurred, although one died and three required amputations; of these, seven are alive and free of disease. In the cases with partial regression, the tumors all recurred and required amputation or other treatment. The most responsive tumor appeared to be melanoma. No conclusions about survivals can be drawn at present although four of seven patients with malignant melanomas treated only by heat perfusion are alive and well with functional limbs 28, 27, 11 and 7 months after treatment. Only one patient has died of metastases although two have been lost to follow‐up.

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