The human gamma delta T cell receptor is normally expressed on lymphoid tissue. Because expression of different molecules of the T-cell system has been described on human brain cells, we examined the expression of T-cell receptor gamma delta antigens with a panel of various anti-gamma/delta TCR mAbs using immunohistochemistry on different regions of frozen human postmortem tissue of five different brains. We found expression of gamma/delta TCR antigens on brain tissue in different regions of the brain, probably on neurons. Using mAbs against the 70-kd human heat-shock-protein (hsp 70), immunohistochemistry showed staining of microglia. A polymerase chain reaction analysis using a highly sensitive primer sequence against the constant region delta sequence supports the notion that the gamma/delta TCR is expressed in human brain; however, the sequence cannot be assigned to a specific tissue with this method. Both heat shock proteins and the gamma/delta TCR seem to be involved in autoimmune processes, and their expression on colocalizing structures in human CNS may play a role in triggering neuropsychiatric autoimmune disorders.