Measurements of height, weight, skinfolds and waist girth were used as indicators of general and regional obesity in the Framingham study population of 5,209 men and women. Mean values of cholesterol, blood pressure, blood glucose and uric acid increased with increasing body mass index (BMI). Weight gain was associated with increases and weight loss with decreases in these risk factors. Cigarette smoking was more prevalent in men and women with low quintile BMI. Upper quintile values of BMI, subscapular skinfolds, and waist girth were associated with increased relative risks of death from all causes, coronary heart disease (CHD) and cerebrovascular disease but relative risks for intermittent claudication were not increased. General and central obesity each made independent contributions to risk of CHD but central obesity was a better predictor in males. BMI, cholesterol, systolic blood pressure and blood glucose were significantly independent predictors of CHD. These data show that increased relative weight and central obesity are associated with elevated levels of risk factors, with increased incidence of cardiovascular disease and with increased death rates for all causes combined. Mortality rates are also increased among the leanest members of the population, especially among older men.