The primary goal of this project is to develop equipment and techniques to be used in the hyperthermic treatment of neoplasms in human patients. Investigation into the non-thermal effects of ultrasound (US), microwaves, and radiofrequency (RF) will be carried out. Special interest will be paid to detection of non-lethal effects of US, microwaves, and RF, such as transformation and cell cycle effects. Thermal distributions in tumors and normal tissues during heating with US, microwaves and RF will be done in dogs and pigs. Changes in blood flow in tumors and normal tissues during and after heating will be studied in mice and larger animals. The time course and magnitude of induced thermotolerance will be investigated in vivo for tumor and normal tissues in mice and pigs. Emphasis will be put on detecting ways to manipulate thermotolerance for maximum normal tissue sparing and tumor toxicity. Morphological studies of heat treated tumors and normal tissues in mice will be investigated. Normal tissues of pigs exposed to US, microwaves, or RF induced hyperthermia will also be studied morphologically. Because of the success of the isospherical ultrasonic hyperthermia system; design studies, initial hardware fabrication and microprocessor control of the transducer assembly will be carried out. Research and development of microwave and RF heating systems will also continue. A controlled trial of hyperthermia and x-irradiation using the isospherical ultrasound system in selected human subjects will be carried out.