The Multiple Risk Factor Intervention Trial (MRFIT) was a randomized primary prevention trial to test whether a special intervention (SI) program to reduce high blood pressure, elevated blood cholesterol, and/or cigarette smoking could lower coronary heart disease (CHD) mortality in middle-aged men at above average risk. After an average follow-up period of 7 years, risk factor levels were reduced substantially more in SI than in usual-care (UC) men; however, SI-UC differences in CHD mortality (7.1%) and total mortality (-2.1%) were not statistically significant. Subgroup analysis showed 35% fewer SI than UC CHD deaths (P = 0.14) but no all-causes mortality difference in men comparable to the cohort having dietary and smoking intervention in Oslo (the "Oslo-like" cohort). Among the subgroup hypertensive at entry, SI-UC differences in CHD and total mortality appeared to be heterogeneous: CHD mortality was 24% lower in SI than UC men with a normal resting ECG at baseline, but 67% higher if baseline ECG abnormalities were present (nominal P = 0.02, for difference in relative risk estimates). These findings were supported by within-group analyses and are generally consistent with results of other CHD/cardiovascular disease prevention trials. They pose a new hypothesis about possible adverse effects of diuretic therapy in a minority of the hypertensive population.