To determine the prevalence of Treponema pallidum in cerebrospinal fluid (CSF) of patients with syphilis, to determine the effect of concurrent HIV infection on central nervous system involvement by T. pallidum and to examine the efficacy of conventional therapy for asymptomatic neurologic involvement. Patients: Fifty-eight patients with untreated syphilis who consented to lumbar puncture, representing approximately 10% of new cases of syphilis during the study period. Interventions: Lumbar puncture was done on all patients. Rabbit inoculation was used to test cerebropsinal fluid for viable T. pallidum. Patients with normal fluid received recommended benzathine penicillin therapy according to the stage of syphilis; patients with CSF abnormalities were offered 10-day therapy for neurosyphilis. Conclusions: Central nervous system invasion by T. pallidum is common in early syphilis, and is apparently independent of HIV infection. Examination of the CSF may be beneficial in patients with early syphilis, and therapy should be guided by knowledge of central nervous system involvement. Conventional benzathine penicillin G therapy may have reduced efficacy in patients with early syphilis who are also infected with HIV.