Thermotolerance is a phenomenon in which cells become resistant to elevated temperatures as a result of prior or continuous exposure to hyperthermia. Thermotolerant cells exhibit a decreased slope of the cell survival curve. Recent studies disclosed that thermotolerance developed in rodent tumors and normal tissues as well. Thermotolerance develops during the treatment at a temperature below approximately equal to 43.0 degrees C, or it develops rapidly after the first heat treatment. The decay of thermotolerance is slow and is incomplete over 7 days in many normal tissues, while it appears to be completed in murine tumors. The kinetics of thermotolerance is modified by various factors. In general, the greater the initial heat damage (independently of temperature), the greater is the magnitude of thermotolerance and the longer is the time to reach maximum and the time to decay. Although thermotolerance develops less extensively in cultured cells in low pH medium and the average tumor tissue pH is lower than the normal tissue pH, the magnitude of thermotolerance in tumors thus far examined is at least equal to that in the normal tissues. Data on the interaction between thermotolerance and radiosensitivity are contradictory, although thermotolerance appears to reduce thermal radiosensitization. The kinetics of reduced sensitization is similar to that of thermotolerance. The interaction between chemotherapeutic agents and thermotolerance appears to depend on the drug and the temperature. Experimental data on this topic are still sparse and extensive studies are required.