The induction of thermotolerance was studied in two groups of murine tumors, one able to produce heat shock proteins (HSP) and the other entirely lacking HSP expression in response to various stress inducers. Heat treatments were performed in vitro and the development of thermotolerance was then evaluated in vivo. The data obtained on the death rate of mice inoculated with tumor cells previously conditioned at 42 degrees C for 1 h and then challenged at 45 degrees C for 30 min following 2 h of reincubation at 37 degrees C, show that the rate of survival is far higher in mice inoculated with HSP negative tumor cells. This indicates that a large number of cells able to increase HSP synthesis following stress escape heat killing, whereas cells unable to express HSP after adequate stimuli are less tolerant against heat challenge.