We have investigated the relationship between the synthesis of hsp-40, recently identified as a mammalian homologue of DnaJ protein, as well as hsp-70 and the development of thermotolerance in cells of the mouse squamous cell carcinoma line SCCVII. Thermotolerance as determined by clonogenic survival was induced not only by prior heating at 44 degrees C for 30 min but also by prior treatment with 100 microM sodium arsenite for 1 h and 5 micrograms/ml prostaglandin J2 for 4 h. These treatments concomitantly induced both hsp-70 (p72, inducible form) and hsp-40. The extent of thermotolerance correlated well with the relative amount of hsp-70 and hsp-40. These results suggest that hsp-40 is a good predictor of thermotolerance in addition to hsp-70.