Our aim was to determine the sensitivity of the Murex ICE enzyme immunoassay (EIA) as a screening test for early syphilis and to determine how many additional cases of infection were detected by performing additional tests when requested on clinical grounds. This was an observational study on consecutive patients diagnosed with syphilis in the Department of Genitourinary Medicine, Edinburgh between January 1st 2004 and April 1st 2005. Additional tests were performed on sera that gave a positive or equivocal EIA on screening as well as by clinical request on sera from contacts of syphilis, and those with clinical signs of syphilis. Additional tests included a Venereal Diseases Research Laboratory (VDRL) carbon antigen test, a Treponema pallidum particle agglutination (TPPA) test, INNO-LIA line immunoblot assay, and an EIA specific for anti-treponemal IgM.A total of 105 patients were diagnosed with syphilis: primary (50), secondary (26), early latent (8), and of unknown duration (21). The TPPA was the most sensitive test in primary syphilis and had a sensitivity of 96% (48/50), which was significantly higher (P <0.05) than the sensitivity of 84% (42/50) for the screening EIA: seven of the EIA negatives were detected by EIA-IgM, six by TPPA, five by immunoblot, and two by VDRL. EIA-IgM was negative in six primaries; all were positive by TPPA and immunoblot. We conclude that, in order to maximize the serological detection of primary syphilis a specific EIA-IgM test and a TPPA test should be performed whenever there is a clinical suspicion of primary infection. This is particularly important when an EIA such as Murex ICE is used as a single screening test as it is less sensitive than the TPPA in primary infection.