Ia antigen, encoded within the major histocompatibility complex, plays an important role in the activation of T lymphocytes. Since experimental allergic encephalitis is an essentially T cell-mediated disease, Ia antigen in the central nervous system (CNS) may be pathogenetically relevant. The occurrence of Ia antigen in the CNS of normal rats and of rats with experimental allergic encephalitis was studied by light and electron microscope immunocytochemistry using the monoclonal anti-Ia antibodies Ox 4 and Ox 6. In normal, unsensitized animals a district population of stellate cells in the meninges and some perivascular mononuclear cells in the nervous tissue carried Ia antigen. In rats with experimental allergic encephalitis a dramatic increase of Ia-positive cells was found. In addition to the positive cells found in normal animals, monocytes, macrophages and many lymphocytes in the meningeal perivascular and parenchymal inflammatory infiltrates as well as "activated microglia" stained for Ia antigen. We did not find evidence for Ia expression on endothelial cells, astrocytes or other components of the CNS in either normal or diseased rats.