Cells in the brain express unusually low levels of antigens encoded by the major histocompatibility complex (MHC)^1,2. This is somewhat surprising as class I (H−2) and class II (Ia) MHC antigens have critical roles in immune responses³. The activation of T lymphocytes is associated with the enhanced expression of these antigens and this effect is mediated by a specific T-cell lymphokine, _γ-interferon (IFN-_γ)^4–17. Here we show that IFN-_γ induces a dramatic increase in the expression of H–2 antigens on the cells of the brain. After exposure to IFN-_γin vitro, all surviving cells, including most astrocytes, oligodendrocytes, microglia and at least some neurones, express H–2 antigens. Direct injection of IFN-_γ into the brains of mice indicated that H–2 antigens were also induced in vivo. Furthermore, IFN-_γ induced Ia antigens on a subpopulation of astrocytes. The induction of H–2 antigens by IFN-_γ may render brain cells competent to initiate and participate in immune reactions and may therefore contribute to both immunoprotective and immunopathological responses in the brain.