The clinical presentation, risk factors, laboratory data, and neuroimaging and neuropathological findings in 26 patients with autopsy proved central nervous system (CNS) aspergillosis are reviewed. Eleven patients had hematological malignancies (8 underwent bone marrow transplantation), 8 patients underwent liver transplantation, and 3 patients had acquired immunodeficiency syndrome. Four had illnesses resulting in immunosuppression (systemic lupus erythematosus, infected aortic graft, neuroblastoma, and fulminant hepatic failure). The most common presenting clinical symptoms of CNS aspergillosis were fever and a strokelike syndrome. Risk factors for developing CNS aspergillosis included neutropenia, immunosuppressive therapy, low CD4 counts, and retransplantation. Spinal fluid findings were nondiagnostic. Computed tomograms and magnetic resonance scans of the head showed low-density lesions or hemorrhagic infarctions. Most aspergillosis cases occurred in the setting of widely disseminated disease commonly arising from the lung. Pathologically, multiple areas of necrosis throughout the brain were seen. Aspergillus invasion of blood vessel walls was seen microscopically. Amphotericin B with or without flucytosine was not effective treatment.