The kinetics of thermotolerance, which is defined as the transient resistance to hyperthermia following an initial heat treatment, was studied in a normal tissue system of C3Hf/Sed mice. Hyperthermia was given by immersing animal feet in a water bath at 45.5 ± 0.1°C. A priming dose was followed by various second doses and the treatment time necessary to induce loss of one toe or a greater reaction in half the treated animals, i.e., ${\rm RD}_{50}$ , was determined. The kinetics of thermotolerance was dependent upon the size of priming dose and the duration of the intertreatment interval. Following the first treatment, thermotolerance developed fully within 24 hr. A smaller priming dose was associated with a more rapid development of thermotolerance. Complete decay of the tolerance was not evident in the first 5 days after the priming dose. The magnitude of thermotolerance increased with the size of first dose. The thermotolerance ratio was approximately 4.5 times greater after a primin...