Hepatic epithelial cells become thermotolerant when conditioned with a 30 minute heat-treatment at 43 degrees C. The effect reaches a full amplitude after a 4-8 hour period at 37 degrees C and lasts for more than one day at a level corresponding to a 50-fold increase in cellular thermoresistance. During the development period, electrophoretic patterns of proteins from cells incubated in presence of 35S-methionine reveal an increased synthesis of a small set of proteins with molecular weights of 107, 89, 70, 68 and 27KD. The maximal synthesis of the induced proteins occurs concomitantly with the maximal increase of cell thermotolerance and has returned to normal when thermotolerance levels off. The induction of specific protein synthesis is also observed in other liver epithelial cells of normal and cancerous origins and in freshly isolated hepatocytes. It is suggested that the accumulation of these proteins in the cells plays a role in the process leading to a thermotolerant state.