An adaptive response results in a reduced effect of a high challenging dose of a stressor after a smaller, inducing dose has been applied a few hours earlier. Radiation-induced fibrosarcoma (RIF) cells did not show an adaptive response, i.e. a reduced effect from a high challenging dose (2 Gy) of a radiation after a priming dose (1 cGy) had been applied 4 or 7 h earlier, but cells of a thermoresistant clone (TR) derived from RIF cells did. Since the expression of inducible Hspa (also known as Hsp70) and Hspb1 (also known as Hsp25) was different in these two cell lines, the role of inducible Hspa and Hspb1 in the adaptive response was examined. When RIF cells were transfected with inducible Hspa or Hspb1, both radioresistance measured by clonogenic assays and a reduction of apoptosis were detected. The adaptive response was also acquired by these two cell lines. The inducible Hspa transfectant showed a more pronounced adaptive response than the Hspb1 transfectant. Based on these results, it appears that inducible Hspa and Hspb1 are at least partly responsible for the induction of the adaptive response in these cells. Moreover, when inducible Hspa or Hspb1 was transfected into RIF cells, co-regulation of the two genes was detected. Heat-shock factor (Hsf) was found to be at least partially responsible for the induction of the adaptive response in these cells.