An increase in the synthesis of heat shock proteins that is induced in cells in vitro by hyperthermia or other types of metabolic stress correlates with enhanced cell survival upon further stress. To determine if a similar increase in stress tolerance could be elicited in vivo, rats were made hyperthermic, and then their retinas were tested for sensitivity to light damage. This treatment resulted in a marked decrease in photoreceptor degeneration after exposure to bright light as compared to normothermic animals. Concomitant with such protection was an increase in retinal synthesis of three heat shock proteins. Thus, a physiological rise in body temperature enhances the stress tolerance of nerve tissue, perhaps by increasing heat shock protein production.