Because syphilis can raise the likelihood of HIV transmission and acquisition, syphilis prevention in the USA has the potential benefit of reducing the number of new cases of HIV. We developed a simplified transmission model to estimate the annual number and cost of new, heterosexually-acquired HIV cases in the USA attributable to syphilis. We estimated the number of heterosexual, HIV serodiscordant partnerships in which syphilis was present in 1996. The model included the probability of transmission of HIV (with and without the presence of syphilis) and other parameters based on data from recent literature. Published direct costs (HIV treatment costs including antiretroviral therapy) and indirect costs (e.g., lost productivity) per case of HIV were used to estimate the annual cost of HIV cases attributable to syphilis. The potential savings in averted HIV costs related to syphilis were used to estimate the potential benefits of a syphilis elimination program. In 1996, an estimated 1082 new heterosexual cases of HIV in the USA could be attributed to syphilis. These cases represented direct costs of US$ 211 million and indirect costs of US$ 541 million; yielding US$ 752 million in total costs. Over 15 years, a syphilis elimination program could save over US$ 833 million (discounted at 3% annually) in averted direct medical costs of syphilis-related HIV infections. If the only benefit of syphilis elimination were to prevent new HIV cases attributable to syphilis, a national syphilis elimination program costing less than US$ 833 million would probably pay for itself.