We sought to evaluate the potential interactions between systemic hypertension and blood lipids on the risk of myocardial infarction (MI). Recent evidence suggests that hypertension may interact with other risk factors such as dyslipidemia in the development of coronary heart disease. However, the precise nature of that interrelation remains unclear. We selected 340 cases of first MI and an equal number of age-, sex-, and community-matched controls. Data were collected on a large number of coronary risk factors, and fasting blood samples were obtained. Logistic regression was used to calculate the odds ratio (OR) of nonfatal MI. The age- and sex-adjusted OR of MI was 1.61 (95% confidence interval [CI] 1.15 to 2.25) among treated hypertensives compared with nonhypertensives. Further adjustment for coronary risk factors did not materially alter the results (OR 1.67, 95% CI 1.16 to 2.41). To explore the interrelations among hypertension, lipids, and risk of MI, each lipoprotein parameter was individually added to the risk factor-adjusted multivariate model. The apparent risk associated with hypertension was substantially attenuated by the addition of either high-density lipoprotein cholesterol (OR 1.25, 95% CI 0.82 to 1.90) or triglycerides (OR 1.37, 95% CI 0.91 to 2.05). No significant interactions were found between hypertension and any lipoprotein parameter. These data indicate that the risk of MI associated with treated hypertension may have a lipid mechanism involving high-density lipoprotein cholesterol and/or triglycerides.