Background: There is increasing evidence that many populations in the developing world are in "epidemiologic transition" with the subsequent emergence of more "affluent" disease states. The "Heart of Soweto Study" will systematically investigate the emergence of heart disease (HD) in a large urban population in South Africa. Methods: Part of the conurbation of Johannesburg, South Africa, Soweto is a predominantly Black African community of 1 million individuals. During an initial two year period, all individuals presenting to the local Baragwanath Hospital (3500 beds) with any form of HD will be studied. Demographic and diagnostic coding data in those with pre-established HD will form an abbreviated clinical registry of > 12,000 "prevalent" cases. Similarly, socio-demographic, clinical and diagnostic data (e.g. echocardiography and ECG) in newly diagnosed patients will form a more detailed clinical registry of > 5000 "incident" cases. Sub-studies of the relationship between HIV status and HD and the optimal management of chronic heart failure will also be performed. Results: These data will provide a unique insight into the causes and consequences of a broad spectrum of HD-related conditions in a "developing world" community in epidemiologic transition. Initially documented population rates, in addition to detailed examinations of the underlying risk factors and causes of HD-related morbidity/mortality will provide an important platform for future stages of the study: a community-based, population screening program and culturally specific primary and secondary programs of care. Conclusion: There is an urgent need to systematically track the emergence of HD in the developing world. Initially involving more than 15,000 individuals, the unique Heart of Soweto Study has the potential to provide a wealth of information in this regard.