Over the past 20 years at my institution, 71 patients with invasive necrotizing aspergillosis have been encountered; 42 have shown central nervous system (CNS) involvement by autopsy (40) or surgical biopsy (2). Most non-CNS aspergillosis patients had invasive disease confined to the lung, and only 2 with dissemination to 3 or more organs did not have spread to the CNS. In addition to the expected post-transplantation and hematologic malignancy cases, other risk groups identified included those with chronic asthma and steroid use, acquired immunodeficiency syndrome, thermal burn, hepatic failure, and postoperative infection. Unusual cases manifested with basilar meningitis, myelitis, proptosis caused by sino-orbital disease, or epidural and subdural Aspergillus abscesses. The extent of gross neuropathologic disease ranged from subtle abscesses to massive hemorrhagic necrosis causing herniation and death. In addition to the expected hemorrhagic necrosis, extensive hemorrhage, focal purulent meningitis, and subtle bland infarctions were also seen. Distinctive microscopic findings encountered included 1 case with numerous meningeal granulomas and multinucleated giant cells and 4 cases showing the Splendore-Hoeppli phenomenon. During the same period, single cases of cerebritis caused by morphologically similar fungi (Pseudoallescheria boydii [Scedosporium apiospermum], Scedosporium inflatum, Chaetomium sp) were identified and were indistinguishable from CNS aspergillosis clinically and pathologically.