To determine if multiple risk factor modification favorably alters the rate of progression of coronary atherosclerosis, 300 patients with established atherosclerosis have been randomized into a clinical trial; 155 to usual care and 145 to special intervention. All patients have medical/risk examinations at baseline and annually for 4 years. The special intervention patients undergo aggressive risk factor management with emphasis on lipoprotein modification, dietary management, smoking abatement, blood pressure control, weight loss and increased physical activity. To measure progression of atherosclerosis, a quantitative, computer-assisted coronary arteriographic system was developed to analyze the baseline and 4-year follow-up arteriograms. This procedure uses a catheter with a metallic calibration cylinder at its tip to determine absolute artery size and automated computer edge detection techniques to define the internal border of the artery. The analysis system detects artery borders using changes in cine film density and measures distances between these borders. For each segment the minimum, maximum and mean diameters are measured and percent stenosis and atheroma area calculated. This system provides precise and reproducible measures of coronary artery segment diameter. Using this technique, we estimate a 33% reduction in the rate of coronary artery progression over 4 years, defined as mean segment diameter, can be detected at a power of 0.80 and an alpha of 0.05 (one tailed test) with a sample size of 120 in each of 2 groups.