Adoptive transfer experiments in athymic nude mice demonstrated that the demyelination seen in the central nervous system (CNS) following Semliki Forest virus (SFV) infection was directly dependent upon sensitized T lymphocytes. Antibodies generated during the infection did not seem to be involved in the demyelination, but thymus-dependent antibodies (IgG) were responsible for the reduction of brain virus titres. In the absence of a T cell response and T cell-dependent antibody production, virus persisted in the CNS for several months. Despite persistence of high virus titres for this time, only mice eventually developing a CNS inflammatory response developed lesions of demyelination. In the absence of an inflammatory response no demyelination was apparent even after several months of persistent infection. Administration of anti-SFV hyperimmune serum intracerebrally to both infected and control mice did not produce demyelination but resulted in CNS tissue degeneration with marked pycnosis.