Forty-year mortality and its association with entry risk factor levels is reported in men employed in the US Railroad industry within the Seven Countries Study of Cardiovascular Diseases. Cardiovascular risk factors were measured in 2571 men aged 40-59 at entry examination in 1957-1959 and after 5 years. Mortality data were collected during 40 years of follow-up (overall mortality of 83.4%). The main causes of death were coronary heart disease (CHD, 32.9% of all causes using strict criteria), atherosclerotic cardiovascular diseases (including coronary, stroke and peripheral artery diseases, (ACVD), 53.2% of all causes) and cancer (25.1% of all causes). Multivariate analysis showed that age, systolic blood pressure, serum cholesterol and cigarette consumption were strongly and significantly associated with all-cause mortality, coronary mortality and cardiovascular mortality. Multivariate relative risks per 5 years of age were 1.31 for all-causes, 1.32 for CHD and 1.36 for ACVD; per 20 mmHg systolic blood pressure were 1.12, 1.23 and 1.26, respectively; per 1 mmol/l of serum cholesterol were 1.06, 1.18 and 1.14, respectively; and per 10 cigarettes smoked per day were 1.14, 1.12 and 1.13, respectively. During a 40-year period classical cardiovascular risk factors were highly predictive of coronary, cardiovascular and all-cause mortality in a US working population.