We prospectively evaluated the level of human immunodeficiency virus (HIV) type 1 RNA in cerebrospinal fluid (CSF) as a marker of HIV encephalitis. Fifty-two HIV-1-infected patients (41 males and 11 females; mean age, 39 years) were tested for the presence of HIV-1 RNA in plasma and CSF. Samples of CSF were obtained by lumbar puncture to evaluate cognitive deficits, seizures, or fever among these patients. HIV encephalitis was diagnosed in 11 patients (21%), other CNS diseases were diagnosed in 12 (23%), and fever without CNS disease was diagnosed in 29 (56%). HIV-1 RNA was detectable in 92% of the plasma specimens and 75% of the CSF specimens. No significant difference was observed in CSF levels of HIV-1 RNA between patients with or without HIV encephalitis. CSF levels of HIV-1 RNA correlated with plasma levels of HIV-1 RNA (Spearman's rank correlation, +0.31; P = .02) and CSF white blood cell counts (Spearman's rank correlation, +0.4; P < .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 the diagnosis of HIV encephalitis.