Little evidence is available on the strength of the association between ambient air pollution exposure and health effects in developing countries such as South Africa. The association between the 24-h average ambient PM(10), SO(2) and NO(2) levels and daily respiratory (RD), cardiovascular (CVD) and cerebrovascular (CBD) mortality in Cape Town (2001-2006) was investigated with a case-crossover design. For models that included entire year data, an inter-quartile range (IQR) increase in PM(10) (12 mg/m3) and NO(2) (12 mg/m3) significantly increased CBD mortality by 4% and 8%, respectively. A significant increase of 3% in CVD mortality was observed per IQR increase in NO(2) and SO(2) (8 mg/m3). In the warm period, PM(10) was significantly associated with RD and CVD mortality. NO(2) had significant associations with CBD, RD and CVD mortality, whilst SO(2) was associated with CVD mortality. None of the pollutants were associated with any of the three outcomes in the cold period. Susceptible groups depended on the cause-specific mortality and air pollutant. There is significant RD, CVD and CBD mortality risk associated with ambient air pollution exposure in South Africa, higher than reported in developed countries.