Intrathecal synthesis of IgG directed to HIV antigens was investigated by antibody specific index (ASI), affinity-mediated immunoblot (AMI) and Western blot (WB) assay in a group of 88 AIDS patients of which 28 with HIV-associated neurological disorders (HAND), 13 without associated neurological disorders (WAND) and 47 with non-HIV-associated neurological disorders (non-HAND). CD4+ count was above 50 cells/mm3 (CD4+>50) in 30 and below 50/mm3 (CD4+<50) in 58 patients, respectively. A significantly higher frequency for CSF complete anti-gag profile (p<0.001), and for HIV-specific oligoclonal patterns ("mixed" pattern=p<0.01) was observed in HAND as compared to patterns from the other clinical groups. A decrease in complete anti-env, anti-pol and anti-gag reactivity was present in CSF of patients with CD4+<50 as compared to those with CD4+>50. Our findings suggest that AIDS appears to be characterized by an anti-HIV intrathecal humoral immune response which is principally directed to env products with a prevalence of oligoclonal patterns and CSF complete anti-gag profile in HIV-associated neurological involvement.