A decline in an organism's ability to cope with stress through acute response protein expression may contribute to stress intolerance with aging. We investigated the influence of aging on stress tolerance and the capacity to synthesize the 70-kDa heat shock protein (HSP70) in young and old rats exposed to an environmental heating protocol. Livers were assessed for injury and HSP70 expression after heat stress by use of immunohistochemical and immunoblotting techniques. The inducible HSP70 response in the cytoplasm and nucleus was markedly reduced with age at several time points over a 48-h recovery period, although senescent rats were able to strongly express HSP70 early in recovery. Older animals had extensive zone-specific liver injury, which corresponded to the diminished HSP70 response observed in these regions, and a significant reduction in thermotolerance compared with their young counterparts. These data highlight the regional nature of stress-induced injury and HSP70 expression in the liver and the impact of aging on these responses. Furthermore, the results suggest a functional link between the age-related decrements in the expression of inducible HSP70 and the pathophysiological responses to heat stress.