To investigate the epidemiology and clinical spectrum of neurosyphilis in a population with high rates of coexisting syphilis and human immunodeficiency virus (HIV) infection, a retrospective analysis of cases in all San Francisco hospitals from 1985 to 1992 was conducted. Neurosyphilis was defined by a newly reactive cerebrospinal fluid VDRL; 117 patients with neurosyphilis were identified. The median age was 39 years, 91% were male, 74 (63%) were white, and 75 (64%) were HIV-infected. Thirty-eight (33%) presented with an early symptomatic neurosyphilis syndrome. Six (5%) had late neurosyphilis. Thirty-eight (32%) patients were asymptomatic, and 35 (30%) had findings attributable to coexisting neurologic diseases. Patients demonstrated high serum nontreponemal (VDRL) titers (median, 1:128) at neurosyphilis presentation. In contrast to the findings from the preantibiotic era, neurosyphilis was identified in young patients most often with HIV coinfection, and early symptomatic syndromes were identified more frequently than late neurosyphilis syndromes.