Two young patients with subacute measles encephalitis are described: a 20-year-old male hemophiliac infected with human immunodeficiency virus (HIV) and a 4-year-old girl with acute leukemia. Both patients were afebrile and had persistent focal seizures and slurred speech beginning 2 and 7 months, respectively, after the onset of uncomplicated acute measles. The diagnosis of subacute measles encephalitis was established by demonstration of paramyxovirus nucleocapsid on electron microscopy of brain tissue in one case and by detection of measles virus genome with the polymerase chain reaction in both. Treatment of the HIV-infected man with intravenous ribavirin was begun when the patient lost consciousness after several weeks of seizures; he died. The girl with leukemia was treated early after the onset of symptoms and recovered after a 15-week course. Review of 31 previously published cases revealed a typical clinical presentation. Cerebrospinal fluid (CSF) analysis, electroencephalography, measurement of measles antibody in serum and CSF, and computed tomography of the brain were not helpful in the diagnosis of subacute measles encephalitis. In contrast, histologic examination of brain tissue proved useful in establishing the diagnosis. On the basis of our experience and our literature review, we conclude that histologic and polymerase chain reaction studies of brain tissue are required for the early diagnosis of subacute measles encephalitis and that therapy with intravenous ribavirin is effective when administered early.