The renewed interest in the possible use of localized hyperthermia in cancer therapy is prompted by two major realizations. The first is the radiobiological evidence indicating that there may be a significant advantage in the use of heat alone or combined with radiation therapy or chemotherapy to enhance the inactivation of tumor cells The second is that early clinical investigation with refractory malignant tumors at temperatures between 41 degrees C and 45 degrees C have shown tumor regression response rate over 70% without increasing normal tissue complication. A phase I/II study using electromagnetic hyperthermia immediately following administration of ionizing radiation was begun at Duke in the fall of 1976 to evaluate the response of normal tissues, the regression of cutaneous and subcutaneous tumors, and the feasibility of such combined modalities in therapeutic radiology. Each hyperthermia session consisted of 45 minutes at 42-43.5 degrees C 2-3 times per week immediately following radiotherapy. The radiation therapy fraction size was usually 2-3 Gy 3-5 times per week with a maximum total of 48 Gy. The 60+ patients treated to date have had squamous cell carcinoma, adenocarcinoma, malignant melanoma, plasmacytoma, liposarcoma, epithelioid sarcoma, and undifferentiated carcinoma. After more than 600 hyperthermia sessions, we have found: (1) local hyperthermia with microwave alone or in combination with ionizing radiation can be used with excellent normal tissue tolerance provided local tissue temperatures are carefully monitored and controlled; (2) a significantly higher level of preferential heat induction into tumor tissue is possible as compared to surrounding normal tissues; (3) repeated hyperthermia at 42-43.5 degrees C for 45 minutes per session immediately following radiation therapy yields favorable therapeutic results. Tumor regression response rate of over 70% was achieved without concomitant increase of normal tissue complication. Therefore, the potentially significant impact on clinical cancer therapy, whether of curative or palliative intent, by moderate thermotherapy is evident. Technical advances to optimize such treatment methods including R & D for delivering a known localized quantity of heat to tumors in any location in the body are expected to progress rapidly. The methods with most promising potential for inducing local thermotherapy are those involving the use of electromagnetic waves, e.g., radiofrequency energy, microwave energy, and ultrasound energy.