The prevalence of neurosyphilis in human immunodeficiency virus type 1 (HIV-1)-seropositive (HIV+) persons was assessed during the course of a study of the neurological complications of HIV-1 infection. One hundred sixty-six asymptomatic HIV+ subjects, 63 neurologically symptomatic HIV+ subjects, and six at-risk HIV-1-seronegative (HIV-) control subjects underwent cerebrospinal fluid (CSF) analysis on entry into this longitudinal study. Three (1.8%) of the asymptomatic HIV+ subjects had both a reactive CSF VDRL test and a reactive CSF fluorescent treponemal antibody-absorption (FTA-ABS) test. Two of these three subjects had a history of appropriately treated early syphilis, and all had a reactive serum rapid plasma reagin test. Of the 63 neurologically symptomatic HIV+ subjects, one patient with dementia had both a reactive CSF VDRL test and a fluorescent treponemal antibody-absorption test. Subjective improvement in cognitive skills followed high-dose, intravenous penicillin therapy. Another subject had a penicillin-responsive myelopathy accompanied by a reactive CSF fluorescent treponemal antibody-absorption test result, but a nonreactive CSF VDRL. Unsuspected neurosyphilis is relatively common in our population of asymptomatic HIV+ subjects and may be responsible for neurological disease in a significant minority of neurologically symptomatic HIV+ persons. Cerebrospinal fluid examination should be performed in all HIV+ persons with a history of syphilis or serological evidence of syphilis, regardless of prior treatment. Additionally, neurosyphilis should be considered in the differential diagnosis of neurological disease in any HIV+ person.