Clinical effects and safety of radiofrequency (RF) capacitive hyperthermia in combination with radiotherapy were evaluated in 40 patients with locally advanced deep-seated tumors. Hyperthermia was administered regionally with an 8-MHz or a 13.56-MHz RF heating device, once or twice a week after irradiation, four to 13 sessions total. Radiotherapy was delivered in fractions of 170 to 200 cGy a day, 5 days a week to 30 to 70 Gy to 33 patients, whereas the remaining seven patients received a total dose of 28 to 60 Gy in fractions of 400 cGy, twice a week. Six of the 40 tumors treated showed CR (100% regression), 6 PRa (80%-100% regression), 13 PRb (50%-80% regression), and 15 NR (less than 50% regression) when assessed by tumor size on computerized tomography (CT) scan. The tumor size before treatment was significantly smaller in CR + PRa tumors than in PRb + NR ones. TDF Time-dose fractionation (TDF) and number of heat treatments, however, did not differ significantly between the both tumors. Greater regression was observed in tumors heated to 41 to 43 degrees C in the maximum temperature than in tumors heated to below 41 degrees C or above 43 degrees C. The minimum tumor temperature was not related to the tumor regression. Posttreatment CT scan revealed remarkable low-density areas in 18 of the 34 tumors that did not regress completely. Histopathologic examinations demonstrated the low-density area to be massive coagulation necrosis and no malignant cell was observed in two tumors examined thoroughly. The types of low-density areas, which were classified according to its percent area in the tumor, correlated with the maximum and minimum tumor temperature. Most of the type III tumors (more than 80% low density) did not regrow in follow-up studies. Complications consisted of subcutaneous fat necrosis in four patients, local edema in four patients, and one abdominal abscess in one patient, all of which eventually resolved. These clinical results strongly suggest the usefulness of RF capacitive hyperthermia combined with radiotherapy for the treatment of refractory deep-seated tumors, and that intratumor low-density areas which appear on posttreatment CT seems to be a good parameter for assessing the tumor response to thermoradiotherapy.