Several recent reports have documented the neuroinvasiveness of human herpesvirus-6 (HHV-6) in infants with primary HHV-6 infections, in children and adults with AIDS, in recipients of bone marrow transplants, and in immunologically intact adults and children. CNS infections with HHV-6 can be subacute and are frequently associated with diffuse or multifocal demyelination. We analyzed the CNS tissues of a young woman who died of a demyelinative disease, which was clinically and histopathologically diagnosed as acute multiple sclerosis, for active HHV-6 infection by immunohistochemical staining. The tissues contained a dense and disseminated active HHV-6 infection that was intimately related to the pathologic changes present.