OBJECTIVE Neuropathological abnormalities induced by HIV-1 are not always predictable on the basis of the presence of HIV-related neurological symptoms. HIV-1 RNA load was measured in the cerebrospinal fluid (CSF) of HIV-infected patients to verify whether it could be a marker of HIV-induced neuropathology. METHODS Histopathological and immunohistochemical examination of the brain for HIV-1 p24 antigen was performed in 50 HIV-infected patients with neurological symptoms; patients were defined as having HIV encephalitis in the presence of HIV-related lesions or HIV-1 p24 antigen-positive cells. Quantitative polymerase chain reaction for HIV-1 RNA was retrospectively applied to CSF samples that had been drawn 1-60 days prior to death from these 50 patients; paired plasma samples of 28 patients were also analysed. RESULTS The CSF HIV-1 RNA copy numbers were significantly higher in 22 patients with HIV encephalitis than in 28 patients without (median, 4.77 log10 versus 3.45 log10 copies/ml; P = 0.0003). No correlation was found between CSF HIV-1 RNA load and the presence of opportunistic brain pathologies at post-mortem examination or between HIV-1 RNA loads in paired CSF and plasma samples. CONCLUSIONS High CSF HIV-1 RNA levels are associated with HIV encephalitis, regardless of the presence of opportunistic brain diseases or HIV-1 RNA levels in plasma. Quantitative CSF HIV-1 RNA may therefore be used as a specific marker of HIV-induced neuropathology.