The present series of experiments was undertaken in an effort to delineate those aspects of ultrasonic irradiation that might be destructive to malignant tumors of bone. The experiments were performed on rabbits having Vx-2 carcinoma implanted within the tibias. In preliminary, experiments, it was shown that the destructive effect of ultrasound on normal bone and on the circulation through normal bone was probably primarily due to heat. In the current series of experiments, it was shown that the heating of the bone was critically dependent on the exact location of the focus of the ultrasonic transducer within the rabbit leg. Our experiments suggested that (1) exposure of Vx-2 carcinoma to a temperature of 50°C for at least 10 min is sufficient to destroy the transmissible characteristics of this tumor, (2) exposure of Vx-2 carcinoma to ultrasonic fields with intense cavitation (applied in the absence of heat) has an effect that is far less than that of heating to 50°C for 10 min, and (3) controlled ultrasonic heating can increase the temperature of a bone to levels sufficient to destroy tumor growth within the bone.