The relation between family history of acute myocardial infarction (AMI) and the risk of AMI was analyzed using data of a case-control study conducted in Argentina between 1992 and 1994. Case patients were 1,060 subjects with AMI admitted to 35 coronary care units, and controls were 1,071 subjects admitted to the same network of hospitals where cases had been identified, for a wide spectrum of acute conditions unrelated to known or likely risk factors for AMI: 31% of cases versus 15% of controls reported > or = 1 first-degree relative with history of AMI. Compared with subjects without family history of AMI, the odds ratio (OR) of AMI, after allowance for age, sex, cholesterolemia, smoking, diabetes, hypertension, body mass index, education, social class, and physical exercise, was 2.18 (95% confidence interval [CI] 1.74 to 2.74) for those with family history of AMI. The OR was 2.04 (95% CI 1.60 to 2.60) for subjects with 1 relative, and 3.18 (95% C 1.86 to 5.44) for those reporting > or = 2 relatives with AMI. In women the OR for any family history of AMI was 2.83, and in men 2.01. The association was of similar magnitude if the mother (OR 1.98), the father (OR 2.13), or a sibling (OR 2.48) had had an AMI. The association with family history was stronger at a younger age because the OR for subjects reporting > or = 2 more relatives with a history of AMI was 4.42 for subjects aged or = 55 years. The association between AMI and family history of AMI was consistent across separate strata of education, social class, smoking, and serum cholesterol, but was less strong in subjects with history of diabetes and hypertension. When the interaction of known risk factors with family history of AMI was analyzed, hypercholesterolemia, hypertension, and smoking had approximately multiplicative effects on the relative risk. The OR was 4.50 for subjects with family history and cholesterol > or = 240 ml/dl, 4.52 for those with hypertension, and 5.77 for current smokers with family history of AMI. Thus, this study confirms that a family history of AMI is a strong and independent risk factor for AMI. In this population from Argentina, family history accounted for 14% of all cases of AMI in men and 26% in women.