After intracerebral inoculation of Borna disease virus (BDV). Lewis rats develop a persistent infection of the central nervous system which is pathohistologically represented by perivascular encephalitic lesions predominantly in the grey matter. In previous studies it has been shown that a cell-mediated immune response causes Borna disease (BD). In order to define further the immune cell responsible for this immunopathological disease, a BDV-specific T cell line, NM1, was established and cultured in vitro. Phenotypically this T cell line was characterized by cytofluorometry as CD4-positive (CD4+). Proliferation assays with syngeneic and allogeneic antigen-presenting cells, and blocking experiments with monoclonal antibodies, revealed major histocompatibility complex class II antigens to be restriction elements. After passive transfer of this virus-specific CD4+ T cell into immunosuppressed BDV-infected recipients, full-blown disease could be induced. Immunohistological examination of the cells involved in perivascular inflammatory infiltrates in BDV-infected rats and in recipients of the NM1 T cell line revealed a dominance of macrophages and CD4+ T cells. The presence of these cells in encephalitic lesions strongly suggests a delayed type of hypersensitivity reaction as the pathogenetic mechanism of BD.