The magnitude of thermotolerance and rate of tolerance decay has been evaluated in three cell lines following isotime and isoeffect initial heat treatments at 44 degrees C. Following the development of maximal thermotolerance, all cell lines lost tolerance at an exponential rate. However, for the three cell lines examined, V-79, CHO, and A-7, differences were apparent in the time required for maximal tolerance development, magnitude of induced tolerance, and rate of tolerance decay. This variability in the thermotolerance response of cells suggests difficulties which might be encountered if in vivo fractionation protocols are to be developed to minimize damages to normal tissue and maximize damages to tumor tissue.