Although coronary heart disease (CHD) is extremely common in South African Indians, there is little published data on the possible causes leading to myocardial infarction (MI) in young Indians. The aim of this study was to identify common environmental risk factors and to examine the relationship between two polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, the 677 C right arrow-hooked T and 1298 A right arrow-hooked C in young South African Indians with MI. Demographic and risk factor data were obtained from245 patients </= 45 years with MI who were admitted to the RK Khan Hospital, Durban. Venous blood from 195 of the 245 patients with MI, as well as from the sublings of the MI patients (n = 107), and 300 healthy age-matched Indian control subjects, were collectd from genetic analysis. Cigarette smoking was the most important risk factor, occurring in three-quarters of patients, followed by dyslipidaemia in half of the subjects. Diabetes (19%) and hypertension (22%) were found not to be major risk factors for MI. A strong familial link was observed not only for a history of CHD (54%), but also for diabetes (42%) and hypertension (41%). No difference was found in the thermolabile variant of the MTFHR gene (677 C right arrow-hooked T) or the second variant 1298 A right arrow-hooked C between controls and patients with MI or their siblings. The two polymorphisms did not appear to work in synergy, neither was there any relationship to common risk factors for CHD. In conclusion, smoking, dyslipidaemia and obesity were the most common phenotypic risk factors for MI. Neither the 667 C right arrow-hooked T nor the 1298 A right arrow-hooked C MTFHR variants appeared to be risk factors for premature CHD in this group.