The effect of hyperthermia on the blood flow was studied in skin, muscle, and Walker 256 carcinoma implanted in the legs of SD rats. The radioactive microsphere method was used to measure the blood flow. Hyperthermia for 1 hour with water at 43 degrees C increased the blood flow in skin and muscle by about threefold to fourfold. On the contrary, hyperthermia had no appreciable effect on the blood flow in tumors. Consequently, during hyperthermia blood flow in the skin and muscle surrounding the tumors was greater than that in tumors larger than about 2 g. Despite the apparent increase in heat dissipation by the increased blood flow, the temperature of the skin was 42.6-42.8 degrees C, and the temperature at the core of tumors larger than 2 cm in diameter was 42.3-42.7 degrees C during the hyperthermia. The lower temperature in the muscle could be attributed to an increase in heat dissipation as a result of the increased blood flow. This differential rise in temperature by heating may account in part for the differential effect of hyperthermia on tumors and normal tissues in vivo.