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Background: In southern Africa, a substantial health transition is underway, with the heavy burden of chronic infectious illness (HIV/AIDS and tuberculosis) paralleled by the growing threat of non-communicable diseases. We investigated the extent and nature of this health transition and considered the implications for primary health care.Methods: Health and sociodemographic surveillance started in the Agincourt subdistrict, rural South Africa, in 1992. In a population of 70 000, deaths (n=6153) were rigorously monitored with a validated verbal autopsy instrument to establish probable cause. We used age-standardised analyses to investigate the dynamics of the mortality transition by comparing the period 2002-05 with 1992-94.Findings: Mortality from chronic non-communicable disease ranked highest in adults aged 50 years and older in 1992-94 (41% of deaths [123/298]), whereas acute diarrhoea and malnutrition accounted for 37% of deaths (59/158) in children younger than 5 years. Since then, all-cause mortality increased substantially (risk ratio 1.87 [95% CI 1.73-2.03]; p<0.0001) because of a six-fold rise in deaths from infectious disease affecting most age and sex groups (5.98 [4.85-7.38]; p<0.0001), and a modest increase in deaths from non-communicable disease (1.15 [0.99-1.33]; p=0.066). The change in female risk of death from HIV and tuberculosis (15.06 [8.88-27.76]; p<0.0001) was almost double that of the change in male risk (8.13 [5.55-12.36]; p<0.0001). The burden of disorders requiring chronic care increased disproportionately compared with that requiring acute care (2.63 [2.30-3.01]; p<0.0001 vs 1.31 [1.12-1.55]; p=0.0003).Interpretation: Mortality from non-communicable disease remains prominent despite the sustained increase in deaths from chronic infectious disease. The implications for primary health-care systems are substantial, with integrated chronic care based on scaled-up delivery of antiretroviral therapy needed to address this expanding burden. INSET: Panel: Management of chronic non-communicable disease in Agincour. [ABSTRACT FROM AUTHOR]