Intracranial inoculation of immunocompetent mice with lymphocytic choriomeningitis virus (LCMV) induces a fatal neurologic illness. In this disease a marked increase in MHC class I expression was found, closely associated with viral antigens and inflammatory infiltrates, in meninges, choroid plexus and ventricular ependyma but not within the brain parenchyma. Immunosuppression prevented MHC induction. Mice inoculated at birth had persistent infections, with LCMV antigens found primarily in neurons, but no inflammatory cells or focal increase in MHC class I. Failure of infected neurons to express MHC class I allows them to escape destruction by cytotoxic T cells (CTL) but may increase their susceptibility to be persistently infected by non-lytic viruses.