For decades, dietary cholesterol has been recognized as the "materia peccans" (Anitschkow) for the induction of atherosclerosis in animals. In rabbits, chickens, and monkeys, long-term feeding of small amounts of cholesterol leads to atherosclerosis despite little or no rise in serum total cholesterol, indicating an independent contribution of dietary cholesterol to atherogenesis over-and-above its influence on serum cholesterol, possibly through effects on serum cholesterol fractions (eg, increased low-density lipoprotein-cholesterol and decreased high-density lipoprotein-cholesterol). In humans, ingestion of dietary cholesterol raises serum cholesterol, largely through its effect on low-density lipoprotein-cholesterol. Over the range of intake in usual American diets, this effect is substantial, eg, with 300 mg of cholesterol intake per 1000 kcal, rather than 100, serum cholesterol is on average about 6% to 7% higher, equivalent to a 12% to 14% greater risk of coronary heart disease (CHD). In international studies based on the Food and Agriculture Organization and the World Health Organization (Geneva) data, mean per capita dietary cholesterol levels are consistently related to CHD mortality rates. In addition, since 1981, four prospective within-population studies have shown that dietary cholesterol intake of individuals is significantly related to their long-term CHD risk, independent of and in addition to serum cholesterol, blood pressure, and cigarette use. On average, a 200-mg/1000 kcal higher intake of cholesterol at baseline was associated with a 30% higher CHD rate (95% confidence interval, 1.1 to 1.5). Conversely, lower intakes of cholesterol were associated with significantly lower risks of CHD, and of all causes mortality as well. For example, with 19 years of follow-up in the Chicago Western Electric Study, a 200-mg/1000 kcal habitual lower cholesterol intake was associated with a 37% lower risk of death from any cause, equivalent to a life expectancy longer by 3.4 years. The importance of a low-dietary cholesterol intake for prevention of CHD merits increased emphasis.