The bovine eye lens protein αA-crystallin has been overexpressed both by stable transfection of HeLa cells and by transient transfection of NIH 3T3 cells. In both experimental systems αA-crystallin overexpression results in an increased cellular thermoresistance as judged by different clonal survival assays. In contrast, similar overexpression of another stable lens protein, βB2-crystallin, does not confer thermoresistance. These results indicate that the structural relationship of αA-crystallin to the small heat shock proteins HSP25/27 and to αB-crystallin is sufficient for the shared thermoprotective function of all of these molecules and strongly suggests that the chaperone-like properties that they have in common are responsible for the conferred cellular thermoresistance.