The effect of hypo to hyperthermic temperatures on tumor blood flow and hypoxic cell fractions was studied in a murine fibrosarcoma transplanted in the hind leg of anesthetized mice. The blood flow to the tumor was assessed by the determination of the uptake of Thallium-201; the hypoxic cell fraction was estimated from cell survival curves derived from data based on lung colony assay. Over a temperature range of 18 degrees to 46 degrees C, the maximal blood flow occurred at 35 degrees C which was approximately two times greater than that at room temperature (24 degrees C) or at 39 degrees C. The hypoxic cell fraction at 35 degrees C was 11%, and was significantly less than that at 24 degrees C or at 39 degrees C. The hypoxic cell fractions at 24 degrees C and at 39 degrees C were 45% and 32%, respectively. These results suggest that the optimal radiation sensitivity of peripherally located tumors can be obtained by warming the tumors to temperatures where maximal blood flow and minimal hypoxic cell fraction occur.