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Syphilis remains a significant cause of morbidity in many developing countries and in some areas within North America and Europe. Mathematical models of the transmission dynamics of sexually transmitted infections have provided insights of relevance both to the interpretation of observed epidemiological patterns and to the design of control programs. Their use for the study of syphilis has been limited to date.The authors investigated the trans-mission dynamics of syphilis against a template based on the natural history of infection in individual patients with the aim of (1) identifying gaps in our understanding of the biology of infection, and (2) providing insights of relevance to the design of control policies.Analyses reveal thatTreponema pallidumhas a moderate to high probability of transmission during contact between susceptible and infectious sexual partners. This, combined with questions over the existence of any immunity to reinfection, helps to ensure the long-term persistence of syphilis within “core” activity groups. Patterns of treatment in North America are shown to have significantly altered the relative frequency of individuals in the different stages of disease.The analyses emphasize the benefits to be gained from treating infected people early in the primary stage of infection to reduce the effective period during which infected people can transmit to others. This form of treatment is beneficial for both the individual and the community. Treatment has greatly altered the incidence of different disease stages, but the full implications of treatment depend on whether immunity is present.