While the inverse association between physical activity and coronary heart disease risk is well documented, questions remain regarding the intensity of exercise, the potential for confounding by other risk factors for coronary heart disease, and the role of blood lipids and apolipoproteins. The authors examined these issues in the Boston Area Health Study, a case-control study of 340 patients (266 men, 74 women) who survived a first myocardial infarction between January 1, 1982, and December 31, 1983, and 340 controls matched on sex, age, and residence. The relative risk of myocardial infarction for those in the highest quartile of physical activity, compared with the lowest, was 0.50 (95 percent confidence interval (CI) 0.31-0.80) for men and 1.00 (95 percent CI 0.41-2.43) for women. When subjects were categorized by level of energy expenditure on moderate to vigorous sports alone, men in the most active category had 0.39 (95 percent CI 0.23-0.69) times the risk of those in the least active category, and women, 0.43 (95 percent CI 0.15-1.26) times the risk. Adjustment for body mass index, smoking, alcohol intake, diet, personal and family medical history, and personality type did not substantially change results nor did further adjustment for blood lipids. This was not surprising as total energy expenditure was uncorrelated with blood lipids or apolipoproteins. Moderate to vigorous sporting activity, however, appeared to be directly related to high density lipoprotein (HDL) cholesterol (p = 0.06), especially the HDL2 subfraction (p = 0.10). In these data, findings suggest that physical activity is inversely related to myocardial infarction risk, independently of other risk factors for coronary heart disease.