A central question in population ecology is the role of 'exogenous' environmental factors versus density-dependent 'endogenous' biological factors in driving changes in population numbers. This question is also central to infectious disease epidemiology, where changes in disease incidence due to behavioural or environmental change must be distinguished from the nonlinear dynamics of the parasite population. Repeated epidemics of primary and secondary syphilis infection in the United States over the past 50 yr have previously been attributed to social and behavioural changes. Here, we show that these epidemics represent a rare example of unforced, endogenous oscillations in disease incidence, with an 8-11-yr period that is predicted by the natural dynamics of syphilis infection, to which there is partially protective immunity. This conclusion is supported by the absence of oscillations in gonorrhoea cases, where a protective immune response is absent. We further demonstrate increased synchrony of syphilis oscillations across cities over time, providing empirical evidence for an increasingly connected sexual network in the United States.