OBJECTIVES: IgM antibodies are usually the first to be produced during treponemal infection. Three commercially available enzyme immunoassays (EIA) for detection of IgM antibodies against Treponema pallidum were evaluated. METHODS: Results of the Anti-Treponema-pallidum-ELISA (IgM; Euroimmun), Pathozyme Syphilis M Capture (Omega Diagnostics) and recomWell Treponema IgM (Mikrogen) were compared with those of the T. pallidum particle agglutination (TPPA) and the Venereal Disease Research Laboratory (VDRL) tests for 307 serum samples. RESULTS: The overall sensitivity (95% confidence interval [CI]) of the TPPA was 100% (97.7-100%) compared to 83.3% (76.5-88.8%) of the VDRL, 88.5% (82.4-93.0%) of the Pathozyme, 84.6% (78.0-89.9) of the Euroimmun, and 73.6% (66.1-80.4%) of a modified recomWell test procedure. Specificities were in the range of 91.4-100%. In primary syphilis, sensitivities of the Pathozyme (89.8%; 95% CI, 79.2-96.2%) and Euroimmun tests (81.4%; 95% CI, 69.1-90.3%) were significantly higher (p < 0.05) than the sensitivity of the VDRL test (61%; 95% CI, 47.4-73.5%). IgM EIAs even were positive in some cases of suspected very early infection where the VDRL was non-reactive and the TPPA was indeterminate. CONCLUSIONS: In cases of suspected early infection specific IgM EIAs should be used in addition to other screening tests. The VDRL is not recommended for screening.