The aims of the study were to assess whether Treponema pallidum-specific IgM may provide a useful marker of infectious syphilis in human immunodeficiency virus (HIV)-infected patients, and to compare the performance of a prototype IgM-rapid point-of-care test (PoCT) with a standard IgM-enzyme immunoassay (EIA). Twenty samples from HIV-infected patients with untreated syphilis (n = 4 primary syphilis, n = 11 secondary and n = 5 early latent) and 51 follow-up samples at three, six or 12 months after treatment were tested for the presence of IgM with the Mercia-EIA (Microgen Bioproducts Ltd, Camberley, UK) and a prototype PoCT (Select Vaccines Ltd, Melbourne, Australia). Although sample numbers were small, IgM detection by EIA appears to be a reliable marker for untreated syphilis in HIV-infected patients with primary (4/4 IgM-positive) or secondary syphilis (10/11 IgM-positive, 1/11 equivocal). After treatment, IgM was no longer detected after three months in the majority of patients (87%) and was either negative or equivocal in all patients after six and 12 months. The overall sensitivity of the IgM-PoCT was 82% and varied with clinical stage, being highest in secondary (10/10 EIA positives) but lower in primary (2/4 EIA positives) and early latent syphilis (2/3 EIA positives). Overall specificity was 95%. Rapid detection of IgM would enable clinicians to distinguish between past-treated and infectious syphilis and allow for diagnosis and treatment in a single visit.