Thermal enhancement of radiation response improved the probability for local tumor control without increasing the risk for late complications in this study of relatively advanced stage tumors. Thirty-eight dogs with naturally occurring oral carcinomas were randomized to two radiation dose response groups to receive radiation alone or combined with local hyperthermia. Radiation was delivered in 10 fractions over 22 days. Heating was done 3 hours after seven of the radiation doses. The objective was to maintain a minimum tumor temperature of 42 degrees C and a maximum normal tissue temperature of 40 degrees C for 30 minutes. Normal tissue temperatures were usually 40 degrees C or less but there was great heterogeneity in tumor temperatures. Temperatures at tumor margins never exceeded 41.5 degrees C. The TCD50 for radiation was 38 Gy (32-46 Gy, 95% C.I.) and for radiation and heat it was 33 Gy (30-36 Gy, 95% C.I.). The slope of the dose response was much steeper for radiation and heat than for radiation alone indicating that the heterogeneity of tumor response was decreased with heat. All tumors were controlled at 40 and 45 Gy with heat whereas only 57% and 75% were controlled with 40 and 45 Gy radiation only. There were no late necroses for radiation and heat. The tumor control enhancement might be improved with different sequences, number of heatings or other time temperature relationships. It is not possible to predict the optimum treatment scheme because of the lack of knowledge of the influence of hyperthermia on subsequent heat or radiation treatments. That influence could be affected greatly by changes in tumor microcirculation, pH, and oxygenation as well as development and decay of thermotolerance in tumor and normal tissue.