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Syphilis control has been the prototypic sexually transmitted disease (STD) public health program of the 20th century. However, the disease remains nearly as much an epidemiologic enigma as it did in the early 1900s. This article examines the historic and epidemiologic bases for syphilis control, using unpublished data to supplement a recent model of STD transmission. The authors recommend building on such traditional individually oriented strategies as case finding, partner notification, and presumptive treatment as a basis for future community-oriented, population-based strategies including (but not limited to) selective mass treatment in high-prevalence populations. Using epidemiologic information to target population-level interventions will be the paradigm for syphilis control in the 20th century.