The astrocyte is thought to be important in AIDS dementia complex (ADC) pathogenesis on the basis of ADC neuropathology and cell culture models putatively because HIV can infect astrocytes leading to a compromise of their physiological detoxifying and neuronal support functions. Confirmatory in vivo data are lacking. Currently, the only widely available marker of the astrocyte is the protein S-100β. Objective: The aims of this study were to determine whether cerebrospinal fluid (CSF) levels of S-100β correlate with the presence, severity and rapidity of ADC progression. Study design: Fourty nine CSF samples from HIV-1 seropositive individuals with either no ADC (ADC stage 0) or varying degrees of ADC (ADC stages 1-3) were analysed in this study. An immunoradiometric assay was used to quantify levels of S-100β in the CSF. All individuals in this study were receiving antiretroviral therapy. In addition, individuals with ADC were grouped as either rapid ADC progressors or slow ADC progressors depending on the period of time from ADC diagnosis to death. Results: CSF S-100β levels in individuals with either ADC stage 2 or 3 were significantly elevated compared to those with stage 0 or 1. Moreover, CSF S-100β levels were significantly higher in individuals with rapid ADC progression compared with slow progressors. Conclusions: This study shows that CSF S-100β levels predict those patients in whom ADC will progress rapidly.