We present the clinical, morphological and neuropathological findings in a 44-year-old male suffering from the acquired immunodeficiency syndrome (AIDS) (CDC stage IV C2) who presented with rapidly progressive right-side hemiparesis and developed hemianopia and aphasia. Scans showed multiple, not contrast-enhancing, not space-occupying echo-intensive lesions in T2-weighted MR-imaging. No hint for an opportunistic infection, necrotizing vasculitis or vascular disease was found. All therapeutic regimens failed and 8 weeks after onset of neurological symptoms the patient died because of cardiorespiratory arrest. Post-mortem examination excluded opportunistic infection, progressive multifocal leukoencephalopathy, lymphoma, vasculitis and ischemia of the brain. In the presence of an unusually high amount of HIV-infected macrophages at immunohistochemical examination, the overall pathological findings were atypical both for HIV encephalitis and HIV leukoencephalopathy. We describe a pathologically distinct new form of HIV associated encephalopathy.