The role of overweight as a risk factor for ischemic heart disease remains controversial. Therefore, in the Manitoba Study of a cohort of 3,983 men with a mean age at entry of 30.8 years, initial measurements of body weight, represented by body mass index (weight/height2), were compared with the 26 year incidence of ischemic heart disease. After adjustment for the effects of age and blood pressure in univariate and multivariate analysis, body mass index was a significant predictor of the 390 cases of ischemic heart disease. To elucidate this relation further, the cohort was further analyzed after categorization by age at entry, time of occurrence of disease after entry and manifestation of ischemic heart disease. The association with weight was most apparent in men less than 40 years of age and was not evident until 16 years of follow-up. A high body mass index was significantly associated with development of myocardial infarction, sudden death and coronary insufficiency or suspected myocardial infarction; the relation was strongest with sudden death. Among men who had a myocardial infarction, body mass index was more strongly associated with sudden death and was the best predictor of myocardial infarction occurring after 20 years of observation. Thus, after adjustment for the effect of age and blood pressure, overweight is a definite risk factor but primarily in younger men, after long periods of observation and for certain manifestations of ischemic heart disease.