During the past few years, evidence has accumulated that interaction with peripheral immune cells as well as immunoregolatory functions in the central nervous system (CNS) can be played by several types of brain resident cells. Since very little information is available in man, however, we investigated the presence of markers so far considered typical of immunocompetent cells in in vitro cultures of human fetal brain. Immunocytochemistry at the light, scanning, and transmission electron microscopic levels revealed positivity for a very restricted range of macrophage antigens in astrocytes, which, however, were incapable of phagocytosis. In particular, expression of the major histocompatibility complex–class II antigen HLADR was observed in the cytoplasm and on the cell surface of GFA‐P⁺ astrocytes and increased with time in culture and cell passages. Among the T‐lymphocyte markers tested, Thy.1 and CD₄ were positive. Both neurons and astrocytes carried Thy.1 from early cell passages. Noteworthy was the presence of CD₄, which serves as the receptor for AIDS virus, in neurons from the first 2 weeks, whereas astrocytes became positive after only 4–6 weeks. Even if most staining was in the cytoplasm, some was exposed on cell surface. Astrocytes were found positive for the B‐lymphocyte marker CD₂₁, the cellular receptor for Epstein‐Barr virus, whereas CD₂₄ was detected in both neurons and astrocytes. Both antigens are related to B‐cell proliferation. Results are in favour of the hypothesis of human brain cells being actively involved in CNS immunological events. © 1992 Wiley‐Liss, Inc.