The heat-shock proteins (hsp) are a family of molecules that have different molecular weights and are thought to operate as scavengers that trap abnormal proteins and protect the stressed cells. These molecules, which have been conserved during evolution, have highly identical stretches of their amino acid sequence in bacteria as well as in humans. Experiments show that arthritis patients manifest T-cell responses to the hsp-65-kD molecule, as do rats with adjuvant arthritis. The B cell response to hsp has not been extensively studied. Autoantibodies against hsp 65, 70, and 90 have been detected in various rheumatic and autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, and inflammatory bowel diseases. The frequency of these antibodies varies among studies and is mainly dependent on the methods of detection. Studies on sensitivity and specificity of these antibodies do not exist; therefore, their significance should be interpreted cautiously.