One hundred eighty-two rats were divided into groups to test the effect of three different total body temperature levels on the toxic effect of three different dose levels of 1.3-bis(2-chlorethyl)-1-nitrosourea (BCNU) and to assess the effect of delayed total body temperature elevation on BCNU breakdown products. Results were tabulated on the basis of life survival figures. At depressed total body temperatures (28° C), normally expected toxicity was avoided. Elevated body temperatures, on the other hand, enhanced the toxic effect of BCNU. Delayed total body temperature elevation (3 and 6 days after BCNU administration) created similar toxicity. This finding was not observed when total body temperature elevation was delayed 10 days. The results point toward an interesting interaction between BCNU and heat (immediate and delayed) on the basis of an elevated metabolic rate of tissue, a synergistic effect of two therapeutic modalities, interference with normal reparative processes by the combination, or an enhancement of retained serum protein-bound breakdown products of BCNU.