To assess the risk of myocardial infarction in users of post-menopausal hormone replacement therapy who are at high risk of coronary disease because of hypertension, diabetes mellitus, or smoking, we used data from a previously published case-control study of women 45-74 years. After adjustment for age, ethnicity, and education, the odds ratio for myocardial infarction in current users of hormone replacement therapy was 0.9 (95% confidence interval (CI) = 0.5-1.6) in women with no major coronary risk factors, 0.8 (95% CI = 0.5-1.8) in women with one risk factor, and 1.1 (95% CI = 0.5-2.2) in women with two risk factors.