The focus here is on relationships between major risk factors and long-term mortality from coronary heart disease (CHD) and all causes, and on longevity, in Chicago cohorts: 25-year follow-up for Peoples Gas (PG) men aged 25-39 (n = 1,119), 30-year follow-up for PG men aged 40-59 (n = 1,235), 24-year follow-up for Western Electric (WE) men aged 40-55 (n = 1,882); also 15-year follow-up for five cohorts of the Chicago Heart Association (CHA) Study: men aged 25-39 (n = 7,873), 40-59 (n = 8,515), 60-74 (n = 1,490), and women aged 40-59 (n = 7,082) and 60-74 (n = 1,243); also 12-year findings for very low risk men (n = 11,098) and other men (n = 350,564) screened for the Multiple Risk Factor Intervention Trial (MRFIT). With a high degree of consistency, multivariate analyses showed independent positive relationships of baseline serum cholesterol, blood pressure and cigarette use to risk of death from CHD and all causes. For the WE cohort, with baseline nutrient data, dietary cholesterol was also independently related to these mortality risks. Combined risk factor impact was strong for both men and women of all baseline ages. Thus, for WE men, favorable compared to observed levels of serum cholesterol, blood pressure, cigarette use and dietary cholesterol were estimated to result in 24-year risk of CHD death 69% lower, all-cause death 42% lower and longevity 9 years greater. For CHA middle-aged and older women, favorable baseline levels of serum cholesterol, blood pressure and cigarette use were estimated to yield 15-year-CHD risk lower by about 60% and longevity greater by about 5 years. For MRFIT, very low risk men (serum cholesterol < 182 mg/dl, systolic/diastolic blood pressure < 120/<80), nonsmokers, nondiabetic, no previous heart attack), compared to all others, observed 12-year death rates were lower by 89% for CHD, 79% for stroke, 86% for all cardiovascular diseases, 30% for cancers, 21% for other causes, 53% for all causes, and longevity was estimated to be more than 9 years longer. These findings indicate great potentials for prevention of the CHD epidemic and for increased longevity with health for men and women, through improved life-styles and consequent lower risk factor levels.