Epstein-Barr virus (EBV) was recovered from cerebrospinal cells (but not from cell-free fluid) of a patient with meningoencephalitis complicating infectious mononucleosis. This finding suggests that virus-altered B lymphocytes can invade the central nervous system and may play a direct role in the pathogenesis of neurologic sequelae of EBV infections. Several mechanisms by which these cells can cause neurologic manifestations are discussed.