The rate of syphilis/HIV co-infection amongst men who have sex with men (MSM) in large urban regions ranges from 20 to 70% (7). Concurrent HIV infection can alter the clinical presentation of syphilis, the response to treatment, and complicate the diagnosis and clinical course of neurosyphilis (18). Therefore whether to perform a lumbar puncture (LP) on every co-infected patient in order to diagnose neurosyphilis is controversial. Current clinical guidelines specify the indications for LP, but fall short of recommending LP in certain clinical situations such as early syphilis without neurological involvement. This article reviews the current literature on the relative utility and indications for LP in syphilis/HIV co-infected patients and new research in this area. SYPHILIS IN THE PRESENCE OF HIV INFECTION The clinical features of syphilis are altered by concomitant HIV infection. HIV co-infection is associated with multiple chancres in primary syphilis and multiple concomitant genital ulcers in secondary syphilis (33), increased frequency of acute syphilitic meningitis in early syphilis (18), high rapid plasma reagin (RPR) titres, rapid progression to tertiary disease, increased ocular disease (uveitis, keratitis, optic neuritis, conjunctivitis, optic atropy, chorioretinitis), delayed or failed normalisation of cerebrospinal fluid (CSF) markers after treatment, and predilection for the Jarisch-Herxheimer reaction (1, 6, 9, 13- 15, 17, 19, 21, 29, 32, 36). Further, syphilis can relapse following treatment in HIV-infected patients (1-3, 12, 13, 17, 19, 29, 30, 32, 35). The pathogenesis of these clinical features may be related to the incomplete clearance of the spirochete from the central nervous system (CNS) because of relative immunodeficiency (22, 30). Therefore, excluding neurosyphilis by CSF examination in co-infected patients becomes more important than in persons with syphilis alone. Syphilis and the CNS Before the advent of penicillin, examination of CSF by LP was performed routinely on patients with syphilis in order to determine the duration of heavy metal therapy (24). Studies from the early part of the century showed CSF abnormalities such as pleocytosis and raised protein concentration in as many as 70% of patients with early syphilis (11, 26, 27, 31, 37) and, importantly, that these findings were predictive of the development of symptomatic neurosyphilis (28). Treponema pallidum invades the CNS in approximately 25% of patients, irrespective of HIV sero-status (32). Neuroinvasion occurs during untreated early syphilis, thence T. pallidum either spontaneously clears from the CNS, persists (asymptomatic syphilitic meningitis) or progresses