Background: Human immunodeficiency virus (HIV) leucoencephalopathy (HIVL) is an uncommon and rapidly progressive form of AIDS dementia complex (ADC) that has remained poorly understood. Tumour necrosis factor α (TNFα ), which has been implicated in the pathogenesis of ADC, is predominantly localised in macrophages in the HIV infected brain, although in vitro studies indicate that neurones can express this cytokine. Objective: To examine the clinical/neuroradiological fea tures of HIVL and the expression of TNFα in HIVL. Methods: Six patients who pr esented with rapidly progressive dementia within four to 12 weeks of the primary manifestation of their HIV infection were evaluated. Clinical history, treatmen t regimens, and imaging studies were reviewed, and brain samples from three of t he patients were studied by means of immunohistochemistry. Results: Imaging stud ies showed diffuse bilateral deep white matter changes in all six patients. Clin ical and imaging abnormalities improved in five of the six patients within weeks after initiation of antiretroviral treatment. Brain biopsies of two showed pron ounced microglia/macro- phage activation, but only scant viral protein (gp41) e xpression. Staining for TNFα was found in microglia/macrophages, and surprisin gly, in neurones also. Postmortem analysis of a third patient also showed TNFα expression in neurones of the frontal cortex and basal ganglia. Conclusion: Thi s study provides the first demonstration of staining for TNFα in the neurones of the HIV infected brain, and suggests that the process underlying this rapidly progressive form of ADC may reflect indirect mechanisms mediated by host factor s, particularly TNFα . Background: Human immunodeficiency virus (HIV) leucoencephalopathy (HIVL) is an uncommon and rapidly progressive form of AIDS dementia complex (ADC) that has remained poorly understood. Tumor necrosis factor α (TNFα), which has been implicated in the pathogenesis of ADCs, is predominantly localized in macrophages in the HIV infected brain, although in vitro studies indicate that the neurones can express this cytokine. Objective: To examine the clinical / neuroradiological feces of HIVL and the expression of TNFα in HIVL. Methods: Six patients who prited with rapidly progressive dementia within four to 12 weeks of the primary manifestation of their HIV infection were evaluated. Clinical history, treatmen t regimens, and imaging studies were conducted, and brain samples from three of t he patients were studied by means of immunohistochemistry. : Imaging stud ies showed diffuse bilateral deep white matter changes in all six patients. Clin ical and imaging abnormalities improve d in five of the six patients within weeks after initiation of antiretroviral treatment. Brain biopsies of two showed pron ounced microglia / macro-phage activation, but only scant viral protein (gp41) e xpression. Staining for TNFα was found in microglia / macrophages, and surprisin gly, in neurones also. Postmortem analysis of a third patient also showed TNFα expression in neurones of the frontal cortex and basal ganglia. Conclusion: Thi s study provides the first demonstration of staining for TNFα in the neurones of the HIV infected brain, and suggests that the process underlying this rapidly progressive form of ADC may reflect indirect mechanisms mediated by host factor s, particularly TNFα.