Two patients with acquired immunodeficiency syndrome (AIDS) who were successfully treated for cerebral toxoplasmosis presented a few weeks later with neurologic abnormalities. Brain CT scan showed ventricular dilatation, ependymitis, and meningoencephalitis. Both patients died despite extensive treatment. Neuropathological examination showed enlargement of the cerebral ventricles, severe ventriculoencephalitis with large ependymal and subependymal necrosis, and numerous pseudomembranes within the ventricle lumen. Microscopic examination revealed severe necrotizing ventriculoencephalitis, meningoencephalitis and myelitis. Immunohistochemical studies revealed the presence of miriads of tachyzoites within and around the necrotic areas. Such form of toxoplasmosis as a diffuse meningo-encephalo-ventriculo-myelitis appear unique to AIDS and, to our knowledge, have not been previously documented.