In the normal human brain, immunoreactive thymosin beta 4, a well-characterized thymic extract, was demonstrated specifically in the cell bodies and processes of a subset of interfascicular and satellite oligodendrocytes with their stained processes terminating around myelin sheaths. Antisera directed against two other thymic polypeptides, thymosin alpha 1 and alpha 7, did not react. In lymphoid tissues, thymosin beta 4 was present in macrophages, Langerhans' cells of the skin, and the interdigitating cells of the thymus. Thus, a subset of oligodendrocytes shares a common antigen of thymic origin with the reticular-dendritic and phagocytic lymphoid cells--all Ia+ immunocompetent cells that participate in the presentation of antigens to T cells. The subset of thymosin beta 4-positive oligodendrocytes is antigenically distinct and may play a role in the immune surveillance of the central nervous system or the demyelinating processes induced by antigen-presenting activated macrophages.