An alteration in the ability of cells to express heat shock proteins could be physiologically important in aging because all living organisms show a reduced ability to respond to stress with increasing age. Using hepatocytes freshly isolated from young adult and old rats, we have shown that the induction of hsp70 expression by heat shock is reduced approximately 50% with age. The decrease in hsp70 expression occurs at the level of transcription and appears to arise from a defect in the heat shock transcription factor. Other investigators have also shown that the induction of hsp70 expression by heat shock as well as other stresses declines significantly with age in a variety of tissues from rats as well as mononuclear cells from human subjects. In addition, a decrease in the inducibility of hsp70 is observed with cell senescence in cultured cells. Therefore, it appears that a reduced ability to express hsp70 in response to stress may be a common phenomenon underlying the aging process.