Objective: To compare the relationship between serum total cholesterol and long-term mortality from coronary head disease (CHD) in different cultures. Design: Total cholesterol was measured at baseline (1958 through 1964) and at 5- and 10-year follow-up in 12467 men aged 40 through 59 years in 16 cohorts located in seven countries: five European countries, the United States, and Japan. To increase statistical power six cohorts were formed, based on similarities in culture and cholesterol changes during the first 10 years of follow-up. Main Outcome Measures: Relative risks (RRs), estimated with Cox proportional hazards (survival) analysis, for 25-year CHD mortality for cholesterol quartiles and per 0.50-mmol/L (20-mg/dL) cholesterol increase. Adjustment was made for age, smoking, and systolic blood pressure. Results: The age-standardized CHD mortality rates in the six cohorts ranged from 3% to 20%. The RRS for the highest compared with the lowest cholesterol quartile ranged from 1.5 to 2.3, except for Japan's RR of 1.1. For a cholesterol level of around 5.45 mmol/L (210 mg/dL), CHD mortality rates varied from 4% to 5% in Japan and Mediterranean Southern Europe to about 15% in Northern Europe. However, the relative increase in CHD mortality due to a given cholesterol increase was similar in all cultures except Japan. Using a linear approximation, a 0.50-mmol/L (20-mg/dL) increase in total cholesterol corresponded to an increase in CHD mortality risk of 12%, which became an increase in mortality risk of 17% when adjusted for regression dilution bias. Conclusion: Across cultures, cholesterol is linearly related to CHD mortality, and the relative increase in CHD mortality rates with a given cholesterol increase is the same. The large difference in absolute CHD mortality rates at a given cholesterol level, however, indicates that other factors, such as diet, that are typical for cultures with a low CHD risk are also important with respect to primary prevention.