Cells that express major histocompatibility complex (MHC) class H molecules can interact directly with CD4 T lymphocytes and either activate immune actions or become the targets of T-cell-mediated cytotoxic attack. Using rat optic nerve cultures combined with immunocytochemistry and in situ hybridization, we have shown that oligodendrocytes, the major myelin-forming cells of the central nervous system and the main casualty of the immune attacks asated with multiple sclerosis and experimental allergic encephalomyelitis, can be readily induced to express MHIC class II mRNA and surface antigens in vito by exposure to y interferon, provided the glucocorticoid dexamethasone is included in the culture medium. Oligodendrocytes exposed to v interferon without dexamethasone fail to express MHC class H molecules, which may account for the failure of previous attempts to induce expression in these cells. In the central nervous system (CNS), the major conditions of this type are multiple sclerosis and experimental allergic encephalomyelitis (EAE). In the normal CNS, cells express MHC class II molecules at low levels, if at all (4). During immunological assault, such as in multiple sclerosis or EAE, MHC class II expression is seen in association with invading monocytes/macrophages and on microglia, which are endogenous to the brain parenchyma but originate from the monocyte/macrophage lineage (4-6). Neurons themselves are considered unable to express MHC class II molecules, and the only macroglial cells implicated in antigen presentation under these circumstances are astrocytes (5-9). These cells and perinatal 0-2A progenitor cells can also be induced to express MHC class II molecules in response to y interferon (IFN-y) in vitro (4,7,(10)(11)(12). In the peripheral nervous system, IFN-y also induces MHC class II expression on Schwann cells, the glial cells of peripheral nerves (13,14). This effect may be of particular relevance in immune-related diseases, such as leprosy (15) Recombinant rat IFN-y and mouse anti-rat IFN-'y antibody (DB1) were provided by P. Van der Meide (24)