Heat shock proteins (hsps) are involved in the response by cells to stress including hyperthermia, hypoxia and injury. Previous work has demonstrated expression of messenger RNA (mRNA) encoding 70 kDa hsps (hsp70) in animal brain in response to stimuli such as these. We have used in situ hybridization histochemistry to assess the distribution and quantity of a specific hsp70 (called hsx70) mRNA in frontal cortex and cerebellum from normal and demented patients whose pre-mortem course had been documented. In cortex, hsx70 mRNA was concentrated over pia mater and glia but was also present over neurons; in cerebellum, hsx70 mRNA was prominent over granule cells but absent from Purkinje cells. Detection of hsx70 mRNA did not correlate with pre-mortem factors such as pyrexia or coma. Increased hsx70 mRNA was found in frontal cortex white matter in Alzheimer's disease and in a mixed group of other neurodegenerative disorders. No changes occurred in cerebellum. The data provide further evidence for altered hsp gene expression in dementia, and support the existence of a stress response occurring in brains affected by such diseases.