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The objective of this study was to characterize the resurgence of infectious syphilis in the United Kingdom between 1997 and 2003.The authors conducted a retrospective analysis of routine surveillance data from genitourinary medicine clinics and data collected through enhanced surveillance.Between 1997 and 2002, diagnoses of primary, secondary, and early latent syphilis made at genitourinary medicine clinics increased by 213% in heterosexual males, 1412% in men who have sex with men (MSM), and 22% in females. These increases have been driven by a series of outbreaks, the largest of which were seen in Manchester (528) and London (1222) up to the end of October 2003. All the outbreaks have been geographically localized and the majority of cases occurred in MSM. A high percentage of concurrent HIV infection was reported, and oral sex was often reported as a route of transmission.Syphilis has re-emerged in response to behavior change, probably driven by changes in the HIV epidemic. The future course of the epidemic is difficult to predict and control remains elusive.