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Astrocytes have been shown to be capable of serving as antigen-presenting cells and as targets for encephalitogenic cytotoxic T lymphocytes. The role of astrocytes in central nervous system (CNS) autoimmune inflammation is unclear. To study this further, we transplanted astrocyte aggregates into the anterior eye chamber of the mouse. The astrocytic nature of these transplants was confirmed by immunohistochemical detection of glial fibrillary acidic protein and the inability to detect oligodendrocyte or microglial markers. When mice bearing transplants were induced to develop experimental allergic encephalomyelitis by either passive or active protocols, the astrocyte transplants developed a perivascular inflammatory response similar to that seen in the host CNS during the course of the encephalomyelitis. The data suggest that astrocytes could serve as targets for the autoimmune attack of experimental allergic encephalomyelitis and support the possibility that the pathogenesis of this disease may involve an autoimmune reaction against a site other than the myelin sheath.