No cerebrospinal fluid (CSF) abnormalities are found in HIV-positive patients in long-term follow-up after standard syphilis treatment. Syphilis has been reported to have immunological effects on HIV infection and HIV is known to modulate both the manifestations of syphilis and the serological response to therapy. HIV-positive patients who had been diagnosed with and treated for syphilis prior to 2007 were identified. Patients were consented for lumbar puncture. Serum HIV viral load, CD4 count and CSF were recorded. Thirty-five patients with previously diagnosed and treated syphilis underwent lumbar puncture. Thirty-four patients had a normal neurological exam. Only one patient had an abnormal mean white cell count (10.7 cells per high-power field). The finding that those with previously diagnosed syphilis had normal CSF and clinical findings is reassuring and supports the practice of using standard syphilis therapy in HIV-positive patients.