Increasing evidence suggests an important role of CD8(+) cells in the pathogenesis of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). In our present study we analyzed the spatiotemporal expression pattern of the CD8 antigen in various rat EAE models characterized by a different extent of inflammation, demyelination, and axonal injury. Unexpectedly, in chronic demyelinating EAE induced by immunization against myelin oligodendrocyte glycoprotein (MOG) the majority of CD8 immunoreactivity was expressed on ED1(+) microglia/macrophages whereas only limited CD8(+) T-cell infiltration was present. CD8(+) phagocyte recruitment was restricted to sites of severe inflammatory tissue destruction. Contrastingly, macrophages in a perivascular or submeningeal position and in secondarily degenerating fiber tracts were mostly CD8(-). CD8(+) phagocytes were absent in myelin basic protein-induced EAE characterized by a purely inflammatory pathology and lack of demyelination. Our data demonstrate significant heterogeneity of lesion-associated phagocytes in rat models of central nervous system autoimmune disease and suggest a specific role of CD8(+) microglia/macrophages in the pathogenesis of inflammatory tissue damage.