The human gamma delta T cell receptor (TCR) is normally expressed on lymphoid tissue. Since expression of different molecules of the T cell system has been described for human brain cells, we examined the expression of CD4 and TCR gamma delta antigens with a panel of various anti-gamma delta TCR monoclonal antibodies (mAbs) and an anti-CD4 mAb using immunohistochemistry on different regions of frozen human postmortem tissue from five different brains. We could confirm the expression of CD4 antigens. gamma delta TCR expression on brain tissue was found in different regions of the brain by immunohistochemistry. Double staining with anti-gamma delta TCR and antineuronal enolase (NSE) mAbs showed that gamma delta TCR+ cells were not stained by anti-NSE, although they were sometimes located near neurons and showed dendritic forms; they are possibly tissue-resident gamma delta T cells, as described in the skin. Polymerase chain reaction analysis using a highly sensitive primer sequence against the constant-region delta sequence supports, combined with immunohistochemistry findings, the notion that the gamma delta TCR is expressed in human brain.