In 1972, the Brisighella Study was initiated to monitor the spontaneous trend of risk factors for atherosclerosis and the incidence of coronary heart disease (CHD) in a rural population. This study, which is one of the largest Italian studies on the epidemiology of atherosclerosis and cardiovascular disease, established a strong correlation between increased cholesterol levels and the incidence of CHD. The apparent unwillingness of the population to alter dietary and exercise habits independently led the researchers to establish the Brisighella Heart Study in 1984. This study attempted to reduce the risk of CHD by modifying the population's dietary habits through a nutritional education program. While the nutritional education program succeeded in lowering total cholesterol, a segment of the population still remained at risk. At this point, the high-risk strategy arm of the study was initiated. In 1988, those participants whose total cholesterol level was greater than 239 mg dl-1 were started on a twice-daily regimen of 600 mg of gemfibrozil. The Brisighella Heart Study High-Risk Project will continue for at least 5 years, during which all participants will be followed-up every 6 months and all fatal and non-fatal events will be recorded.