Demographic and lifestyle information from 9690 black patients diagnosed with cancer or cardiovascular disease was collected in an ongoing case -control study in Johannesburg, South Africa. Compared to never smokers, the odds ratio (OR) for lung cancer among current smokers was 16.3 (95% confidence interval (CI), 9.6 -27.6) for men and 6.4 (95% CI, 4.0 -10.4) for women. The corresponding OR for other smoking-related cancers was 4.6 (95% CI, 3.7 -5.7) among men and 1.9 (95% CI, 1.6 -2.2) among women, and for cardiovascular disease, 3.4 (95% CI, 2.1 -5.4) among men and 1.5 (95% CI, 1.1 -2.1) among women. Risks were higher among smokers than former smokers, and all risk estimates increased with increasing levels of smoking duration and intensity. Non-electric domestic fuel was associated with approximately 60% increase in the risk of smoking-related cancer, but not cardiovascular disease. Risks for cancers of cervix, oesophagus, oral cavity/pharynx, stomach, larynx, pancreas and anogenital region, as well as squamous cell carcinoma of skin were all significantly higher among current than never-smokers, with ORs ranging from 1.5 for cervix (95% CI, 1.2 -1.8) to 14.7 for larynx (95% CI, 7.2 -30). The risks of tobacco-related disease reported here are similar to that currently observed in Western countries, even though cigarette consumption is relatively low in this population.