We used a unique data base containing medical family history information from representative Utah families to investigate interactions between diabetes and family history of coronary heart disease and other risk factors for coronary heart disease. We compared nonrelated individuals reported to have had diabetes mellitus diagnosed over the age of 19 (948) with 2150 nondiabetic individuals. Among both men and women, diabetes and family history of early coronary heart disease magnified the risk for coronary heart disease, so that in diabetic individuals with a positive family history of coronary heart disease, about 74% of the coronary heart disease could be attributed to interaction. Relative to nondiabetics without a family history of early coronary heart disease, nondiabetics with family history had a relative risk of 4.5 (2.3–8.7), diabetics without a family history had a relative risk of 2.8 (1.6–4.9), and diabetics with a family history had a relative risk of 21.3 (9.1–50.0). Smoking also interacted with diabetes; among smoking diabetics, 47% of early heart disease may be attributable to interaction between smoking and diabetes. Smoking entailed the highest risk for diabetic women. Hypertension and diabetes appeared to act additively, with little interaction. Among women, family history of diabetes was a risk factor for coronary heart disease with a relative risk of 2.5 (1.0–6.4), whereas for men the relative risk was estimated to be 0.4 (0.2–1.1). (Epidemiology 1990; 1:298–304)