To assess the association between cerebrospinal fluid (CSF) viral load, intrathecal immunoactivation, and immunosuppression in HIV-1-infected individuals with no antiretroviral treatment experience a cross-sectional study of stored frozen CSF and plasma samples were conducted. The study population included a total of 120 antiretroviral-naive HIV-1-infected patients, 110 neuroasymptomatic patients, and 10 with neurologic complications. HIV-1 RNA was quantified in cell-free CSF and plasma using polymerase chain reaction (PCR; Roche Amplicor HIV-1 Monitor version 1.5, Roche Diagnostic Systems, Hoffmann-La Roche, Inc., Base, Switzerland). Immunoactivation was measured by CSF-serum IgG index, CSF neopterin concentrations, and CSF monocytic cell count. The CSF HIV-1 RNA load did not differ significantly between patients with or without neurologic complications. In patients without neurologic symptoms, the CSF monocytic cell counts were correlated to the CSF viral load (r(s) = 0.40, p < .001), whereas IgG index and CSF neopterin concentrations were correlated to the viral load only in the subgroup of patients with CD4 counts > or =200 x 10(6) cells/L. In this subgroup of patients, the peripheral CD4 cell count was, as expected, inversely correlated to the CSF viral load (r. = -0.36, p < .01), whereas in patients with CD4 counts <200 x 10(6) cells/L, an unexpected, significant positive correlation (r(s) = 0.43, p < .01 ) was found. In HIV-1-infected patients with neurologic complications, no significant correlations were found between immune activation, CSF viral load, and immunosuppression.