the first major U.S. study of the epidemiology of cardiovascular disease, begun in Framingham, Massachusetts, in 1948 under the auspices of the National Heart Institute (now the National Heart, Lung, and Blood Institute) and still in operation. Initially the Framingham researchers enrolled 5209 men and women between the ages of 30 and 60 to study the evolution of heart disease and identify risk factors for heart attack. In 1971, the Framingham Offspring Study enrolled 5,124 adult children of original study participants along with their spouses, and in 2001 the Third Generation Study recruited some 3,500 grandchildren of original enrollees.Framingham, about 20 miles west of Boston, was chosen as the site of this long-term epidemiologic study because it was close to major medical centers and had participated in an earlier population-based investigation of tuberculosis. Participants undergo periodic physical examination, electrocardiography, and laboratory testing. The Framingham study has produced more than 1,000 scientific papers and has had a major impact on the modern understanding of cardiovascular disease and the prevention and treatment not only of heart attack but also of stroke. During the 1960s, cigarette smoking, elevated cholesterol, hypertension, obesity, and lack of exercise were all statistically confirmed to be risk factors for heart attack. In succeeding years, the study provided valuable information on triglycerides, LDL cholesterol, mitral valve prolapse, heart failure, atrial fibrillation, stroke, diabetes, cardiovascular risk factors in ethnic minorities, and the role of estrogen in preventing heart attack in postmenopausal women. The current emphasis is on identifying genetic and molecular risk factors for heart disease and other cardiovascular disorders.