A relationship between cholesterol gallstone disease and atherosclerosis or its sequellae has long been postulated but has never been adequately proven. Data for this investigation of the relationship of diagnosed cholesterol cholelithiasis to subsequent incident coronary heart disease were obtained from a review of the pre-existing prospectively collected medical records of the 5,209 individuals followed since 1952 as members of the original cohort of the Framingham Heart Study. Preliminary univariate examination of these data, making no correction for time ordering of the conditions or for shared risk factors, indicated a significant modest positive association in men but no relationship in women. Logistic multiple regression analyses, allowing for the effects of time ordering and for eight standard coronary disease risk factors, confirmed these findings. The authors speculate that the presence of cholesterol gallstones in male patients may be indicative of an unfavorable lipoprotein profile. These results have clinical implications in that male gallstone patients are at increased risk for subsequent coronary disease and should be monitored accordingly. This investigation marks the first time that a relationship between these conditions has been established using a longitudinal cohort study approach.