Forty-year all-cause mortality and its association with entry risk factor levels are reported for men enrolled in the Italian Rural Areas of the Seven Countries Study of Cardiovascular Diseases. Forty-eight potential risk factors were measured in 1712 men aged 40-59 at entry examination in 1960. Mortality data were collected during 40 years of follow-up. The relationship of entry risk factor levels with all-cause mortality was studied by univariate and multivariate approaches. Overall death rate was 83.7%. The main causes of death were cardiovascular diseases, followed by cancer and others. The 48 risk factors were tested with univariate and multivariate approaches. In the final model, 15 risk factors were strongly and significantly related to all-cause mortality and survival. They were age, father and mother history of premature mortality, cigarette smoking, job-related physical activity (protective), body mass index (BMI) (in an inverse J-shaped fashion), mid-arm circumference (protective), mean blood pressure, forced respiratory volume in 3/4 seconds (protective), serum cholesterol, corneal arcus, xanthelasma, presence of cardiovascular diseases, cancer and diabetes at entry examination. During a 40-year period 15 mainly cardiovascular risk factors were highly predictive of all-cause mortality and survival in middle-aged men.