Cell preparations from Novikoff'epatoma, 5123 epatoma, Ehrlich ascite mous tumor, regenerated' rat liver, rat liver and human tumors were kept at different temperatures (from 38° to 44°C) for 6 hr. The O2 uptake of the cells without and with substrates was measured during and after exposure at the different temperatures. In some ofthe cells, notably those from Novikoff epatoma, exposure at temperatures of 42° and 44°C,produces an irreversible decrease in the uptake of O2, while no change can be observed in the rate of anaerobic glycolisis. The cells from normal tissues do not show such behaviour on heat treatment and it is concluded that the effects reflect a specific sensitivity to heat of indifferentiated tumor cells. On the basis of the findings in vitro, attempts to treat human tumors of upper and lower limbs were made employing regional perfusion with pre-warmed blood, (40.5°-41.5°C). The temperature of the perfused limb rises to about 41.5°-43.5°C and is maintained at this temperature for about 3 hr. The results obtained on 21 patients showed, in all except one, massive necrosis of the tumors; and some satisfactory long term clinical recoveries.