We evaluated prospectively the HIV-1 RNA level in CSF as a marker of HIV encephalitis diagnosis. 110 HIV-1 infected patients (mean age: 39 years; sex-ratio M/F: 94/16) were tested for HIV-1 RNA in plasma and CSF. Lumbar punctures were performed to explore cognitive deficit, seizure or fever. HIV encephalitis was diagnosed in 15 patients (14%), other CNS disease in 34 (31%), and fever without CNS disease in 61 (55%). HIV-1 RNA was detectable in 93% of the plasma and in 62% of the CSF. No significant difference was observed in CSF HIV-1 RNA between patients with or without HIV encephalitis. CSF HIV-1 RNA was correlated with plasma HIV-1 RNA (p < 0.01), CSF protein (p < 0.01) and CSF white cell counts (p < 0.01). The absence of any significant difference between patients with or without HIV encephalitis, suggests that the CSF HIV-1 RNA level is not a good marker for its diagnosis.