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Background. Disease control and preventive interventions should be tailored towards core groups most affected by syphilis and epidemic phase, which requires correctly identifying the groups to whom interventions should be focused and the allocationMoreBackground. Disease control and preventive interventions should be tailored towards core groups most affected by syphilis and epidemic phase, which requires correctly identifying the groups to whom interventions should be focused and the allocation of enough resources to reach a sufficient number of those at risk for infection. However, few empirical data exist confirming the theorized role of core groups in initiating and supporting epidemics.-Methods. Syphilis surveillance data were collected from Baltimore, 1994-2004 and San Francisco, 1998-2005. Using logistic regression, reported risk factors among syphilis cases were compared across epidemic phases to determine whether an epidemic inflection point in Baltimore 2002-2004 could be attributable to changes in risk behaviors between or across known core groups. To determine whether concurrent bacterial STIs in men who have sex with men (MSM) with early syphilis was a marker of core group membership, San Francisco data were used to measure gonorrhea and chlamydia prevalence- Predictors of dual infection were assessed using logistic regression. Core group size was estimated using a simple, deterministic mathematical model of syphilis transmission among MSM- the model was validated using the San Francisco data.-Results. Analyses confirmed that Baltimores increased incidence is attributable to increases among MSM and young women involved in commercial sex work rather than a reversal of prevention efforts among African Americans. San Francisco data show significantly higher prevalences of gonorrhea and chlamydia among cases diagnosed in the public health setting (17% and 14%, respectively) compared to those diagnosed in the private setting (1% and 1%). Methamphetamine [aOR: 1.85] and other stimulant use [aOR: 1.97] were independently associated with dual infection, indicating that dual infection is an appropriate marker of core group membership. The mathematical model predicted that a core group that was 1.0-3.5% of the total MSM population was sufficient to support a large syphilis epidemic, although the models predicted incidence diverged from the observed incidence in the epidemics later years.-Conclusions. Relatively simple analyses performed on syphilis surveillance data elicit important information regarding epidemic inflection points and core group characteristics- however, the limitations of the transmission model underscore the need for more data on MSM sexual networks.