To assess the impact of serum cholesterol level on the risk of fatal coronary heart disease for men with high blood pressure, the six-year follow-up data from 361,662 men (aged 35 to 57 years) screened in 18 cities in the recruitment effort for the Multiple Risk Factor intervention Trial were evaluated. Of these men, 356,222 reported no history of hospitalization for myocardial infarction; 100,032 of these 356,222 had a baseline mean diastolic blood pressure equal to or greater than 90 mm Hg. For those men with high blood pressure, the overall age-adjusted six-year rate of coronary heart disease death was 79 percent higher than for those with diastolic blood pressure less than 90 mm Hg. Compared with men with diastolic blood pressure less than 90 mm Hg and serum cholesterol below 182 mg/dl, men with diastolic blood pressure equal to or greater than 90 mm Hg had the following relative risks, based on the serum cholesterol level: for those with a serum cholesterol level less than 182 mg/dl, risk was 1.64; for those with a level of 182 to 202 mg/dl, risk was 2.14; for those with a level of 203 to 220 mg/dl, risk was 3.14; for those with a level of 221 to 244 mg/dl, risk was 3.29; and for those with a level equal to or greater than 245 mg/dl, risk was 5.14. Thus, for men with high blood pressure, serum cholesterol related to coronary heart disease risk in a strong, graded way, over the entire distribution of serum cholesterol, from levels of 182 mg/dl and higher. This was the case for hypertensive male smokers and nonsmokers, with cigarette use associated with a further marked increase in risk-at least a doubling of the mortality rate-at any level of serum cholesterol. These data underscore the necessity for a strategy of comprehensive care for persons with high blood pressure, including approaches to both nutritional and hygienic counseling and drug treatment, aimed at controlling all of the established major risk factors influencing prognosis.