BACKGROUND Complications of Epstein-Barr virus (EBV) infection are diverse and include a number of neurologic manifestations such as meningitis, meningoencephalitis, cerebellitis, cranial neuritis and others. In general encephalitis caused by EBV in pediatric patients has been considered a self-limited illness with few or no sequelae. METHODS Charts were reviewed from all patients < 18 years of age admitted to or discharged from the State University of New York Health Science Center at Syracuse between 1982 and 1992 with a diagnosis of encephalitis or meningo-encephalitis. Eleven cases of EBV encephalitis diagnosed during a 10-year period were reviewed to characterize the clinical and laboratory findings in the acute setting and the extent of neurologic sequelae on follow-up. RESULTS Acute neurologic manifestations were diverse and included combative behavior (55%), seizures (36%), headache (36%) and evidence of focal involvement (27%). Classic findings of infectious mononucleosis were noted infrequently; 18% each had pharyngitis, adenopathy, positive heterophile antibody tests or atypical lymphocytosis. Two patients (18%) had abnormal neuroimaging studies, one in the acute stage and the other at the time of follow-up. Seven patients (64%) had abnormal electroencephalograms (EEGs) in the acute setting; of these three had persistent abnormalities on follow-up. Forty percent developed persistent neurologic abnormalities including global impairment, perseverative autistic-like behavior and persistent left upper extremity paresis. CONCLUSIONS Classic signs, symptoms and laboratory findings in infectious mononucleosis may be absent in Epstein-Barr virus encephalitis. Neurologic sequelae occur in a substantial number of patients.