The levels of antibodies to HIV-1 and the occurrence of HIV-1 were determined in the cerebrospinal fluid (CSF) and the blood of 60 people in various stages of HIV-1 infection. Intrathecal synthesis of anti-HIV-1 immunoglobulin (Ig) G was detectable at a low frequency in individuals with normal immunological parameters, and in the majority of patients with various degrees of immunodeficiency. The intrathecal production of antibodies to HIV-1 was strongly associated with the recovery of the virus from CSF. A relationship between high anti-HIV-1 IgG levels and occurrence of HIV-1 was also found in blood. Patients without overt neurological symptoms exhibited intrathecal synthesis of anti-HIV-1 IgG as often as those with such symptoms. These findings suggest that intrathecal synthesis of antibodies to HIV-1 is related to a persistent HIV-1 antigenic stimulation in the central nervous system (CNS). HIV-1 often seems to elicit a humoral immune response in the CNS, without concomitant overt neurological symptoms.