We have previously found an increased risk of ischaemic heart disease (IHD) in men with the Lewis phenotype Le(a-b-) and suggested that the Lewis blood group has a close genetic relation with insulin resistance. We have investigated whether any conventional risk factors explain the increased risk in Le(a-b-) men. 3383 men aged 53-75 years were examined in 1985-86, and morbidity and mortality during the next 4 years were recorded. At baseline, we excluded 343 men with a history of myocardial infarction, angina pectoris, intermittent claudication, or stroke. The potential risk factors examined were alcohol consumption, physical activity, tobacco smoking, serum cotinine, serum lipids, body-mass index, blood pressure, prevalence of hypertension and non-insulin-dependent diabetes mellitus, and social class. In 280 (9.6%) men with Le(a-b-), alcohol was the only risk factor significantly associated with risk of IHD. There was a significantly inverse dose-effect relation between alcohol consumption and risk; trend tests, with adjustment for age, were significant for fatal IHD (p = 0.02), all IHD (p = 0.03), and all causes of death (p = 0.02). In 2649 (90.4%) men with other phenotypes, there was a limited negative association with alcohol consumption. In Le(a-b-) men, a group genetically at high risk of IHD, alcohol consumption seems to be especially protective. We suggest that alcohol consumption may modify insulin resistance in Le(a-b-) men.