Antigens shared by the immune and central nervous systems (CNS) have been described repeatedly. The present study reports the expression of the CD6 lymphocyte differentiation antigen in normal human brain evidenced by immunohistochemistry and Northern blot analysis. A panel of various anti-CD6 monoclonal antibodies (mabs) tested on serial cryostat sections identified CD6-positive cells randomly scattered in parenchyma of all examined brain areas. Northern blot analysis with a highly sensitive cRNA probe revealed a 3.1 kb CD6-specific mRNA in various brain regions, especially in basal ganglia and cortex cerebellum. Staining with mabs raised against different hematopoietic cell types, as well as hybridization with probes specific for the beta- and gamma-T cell receptor (TCR) chains support the notion that CD6 is expressed by original brain cells. The nature of the CD6-positive cell type and possible functions of shared antigens in immune and nervous systems are discussed.