The association of viral infections with autoimmune central nervous system (CNS) diseases such as post-infectious encephalomyelitis and possibly multiple sclerosis (MS) prompted the investigation to understand how virus infection could modulate autoimmune responses. Recombinant vaccinia viruses encoding an encephalitogenic portion of myelin basic protein (MBP) were evaluated in an animal model for human demyelinating disease, experimental allergic encephalomyelitis (EAE). We have determined that mice vaccinated with recombinant viruses encoding an encephalitogenic region of MBP were protected from EAE. In vivo depletion of CD8+ T cells did not abrogate this protection, suggesting lack of regulation by this cell type. These studies demonstrate that virus infection may be a means to modulated immune responsiveness to CNS disease.