Granulomatous amebic encephalitis (GAE), or meningoencephalitis due to Acanthamoeba spp. and leptomyxid ameba are uncommon CNS infections that generally occur in immunocompromised hosts. We describe a case of GAE caused by Balamuthia mandrillaris previously designated as a leptomyxid ameba, in an apparently healthy 14-year-old Venezuelan boy. This case was characterized by sudden onset of seizures, focal neurologic signs and by a prolonged clinical course (from November 1992 to March 1993). Neuroimaging studies showed cerebral hypodense lesions in cerebral hemispheres, brain stem and cerebellum. Microscopically, we found a chronic granulomatous inflammatory reaction with necrotizing angiitis, large numbers of amebic trophozoites and few cysts in perivascular spaces and within necrotic CNS tissue. The amebas were identified as B. mandrillaris based on their immunofluorescence reactivity with the anti-B. mandrillaris serum. So far, 30 cases of GAE due to B. mandrillaris have been recognized in humans, two in AIDS patients. No visceral involvement by free-living amebas or any other significant abnormality was observed. This patient developed "spontaneous" GAE, but it remains possible that an undiagnosed abnormality in cell-mediated immunity or a deficient humoral immune response may explain the susceptibility of this patient to this opportunistic infection.