survival of the animals tested (33, 40). Furthermore, the response of Ll2lO leukemia to tumor-inhibitory drugs is considered to be similar to that of many human tumors (18). We have treated the cells in vitro because it was necessary to use temperatures higher than mice can tolerate. The viability of the cells after treatment was assayed by reinoculation into mice, rather than by the dye exclusion test (36) used by von Ardenne and others (2â€”6) in similar experiments. We have found that the viability determined by the dye exclusion method does not agree with the bioassay, which is a more precise and direct method. Experimental studies have shown that some metabolic processes are preferentially affected by heat : respiration (7, 8, 29, 30, 43), DNA synthesis (16, 17, 28, 29), RNA synthesis (28, 29), and protein synthesis (28, 29). Stehlin (41) has demonstrated that the chemotherapeutic effect of phenylalanine mustard, administered by closed circuit perfusion to human melanomas of the limbs, is considerably increased by raising the temperature of the perfusing fluid above 42Â°. These findings have prompted us to investigate more extensively the possibility of using chemicals in combination with heat. We have tested metabolic inhibitors of DNA synthesis [FUDR4 (20, 21)] , RNA synthesis [actinomycin D (23)] , protein synthesis [DHBA (19)1 , glycolysis [DL glyceraldehyde (26, 27), 2-deoxy-D-glucose (10, 46)], sodium oxamate (35), mitotic poisons [vinbiastine (34)1, and an alkylating agent [PAM (1 1, 32)1.