A cell's reaction to heat shock is one of the most conserved responses among evolutionary diverse species. Although selected features of the response may vary between organisms, the synthesis of heat shock proteins is universal. The induction of hsps is rapid and occurs immediately following exposure to only a few degrees above normal physiological temperature. The array of assigned functions as well as those hypothesized for heat shock proteins imply that hsps are designed to render cells capable of coping with a variety of physiological stresses, including heat and oxidative injury. Interestingly, the gene for the hsp70 is located between the complement and tumor necrosis factor genes within the class III region of the human major histocompatibility complex on the short arm of chromosome 6. Hsp70 proteins have been linked with a protective role during stress and as unfoldase(s) in protein translocation into the endoplasmic reticulum and mitochondria. Moreover, hsp analogs are often presented as antigens in bacterial or protozoal infections. The mapping of hsp70 in the MHC region may have significant implications with regard to immune mediated diseases. Moreover, the relationship of hsps to immunity and cancer represents the beginning of a major link of the role of hsps in human pathology. Finally, with its pleiotropic roles in essential cellular physiology and immune function, we predict that future experiments will define a relationship between hsps and allergy.