The Multiple Risk Factor Intervention Trial was a randomized primary prevention trial to test the effect of a multifactor intervention program on mortality from coronary heart disease (CHD) in 12,866 high-risk men aged 35 to 57 years. Men were randomly assigned either to a special intervention (SI) program consisting of stepped-care treatment for hypertension, counseling for cigarette smoking, and dietary advice for lowering blood cholesterol levels, or to their usual sources of health care in the community (UC). Over an average follow-up period of seven years, risk factor levels declined in both groups, but to a greater degree for the SI men. Mortality from CHD was 17.9 deaths per 1,000 in the SI group and 19.3 per 1,000 in the UC group, a statistically nonsignificant difference of 7.1% (90% confidence interval, —15% to 25%). Total mortality rates were 41.2 per 1,000 (SI) and 40.4 per 1,000 (UC). Three possible explanations for these findings are considered: (1) the overall intervention program, under these circumstances, does not affect CHD mortality; (2) the intervention used does affect CHD mortality, but the benefit was not observed in this trial of seven years' average duration, with lower-than-expected mortality and with considerable risk factor change in the UC group; and (3) measures to reduce cigarette smoking and to lower blood cholesterol levels may have reduced CHD mortality within subgroups of the SI cohort, with a possibly unfavorable response to antihypertensive drug therapy in certain but not all hypertensive subjects. This last possibility was considered most likely, needs further investigation, and lends support to some preventive measures while requiring reassessment of others.