The 53-year-old Framingham Heart & Lung Study, whose breakthrough findings have led millions of Americans to change the way they live, has begun recruiting its third generation of participants.

Letters were sent out Wednesday and Thursday to the grandchildren of the original participants, inviting them to continue in the footsteps of their parents and grandparents and take part in the longest epidemiological project in medicine.

The Framingham study is funded by the National Heart, Lung and Blood Institute and staffed largely by doctors from Boston University. It began in the Boston suburb of Framingham in 1948.

Among the study's findings: a link between cigarette smoking and heart disease, the risk of high cholesterol, the dangers of obesity, the benefits of exercise and the dangers of high blood pressure. More than 10,000 people have participated in the study. Its organizers hope to recruit about 3,500 more from the third generation. Volunteers agree to extensive physical exams every three or four years. They also provide information about their eating and living habits.

In return, they get thousands of dollars in free tests and a chance to be part of research that has already produced most of what is known about the causes of COPD, heart attacks and strokes. Adults as young as 20 will be added to a sample with people as old as 90, enabling researchers to chart family risk factors like obesity, high cholesterol, diabetes and asthma through the generations and perhaps determine the role played by genetics and lifestyle in various diseases.