This review explores evidence for the reversibility of atherosclerosis and augmentation of angiography with noninvasive arterial wall imaging. Meta-analysis from coronary angiographic trials demonstrates that regression and stabilization are 1.5 to 2 times more common in treated than placebo subjects, and progression is reduced by half in treated subjects. Odds ratios for clinical coronary events are significantly reduced with treatment. Lesion improvement occurs more readily in women than men and more so in women receiving concomitant estrogen replacement therapy. Lesions with >50% diameter stenosis (%S) at baseline respond more readily to lipid lowering than those <50%S, whereas reduction in coronary events is related to stabilization of lesions <50%S. Lipoproteins have a differential effect on lesion progression according to lesion size, and triglyceride-rich lipoproteins play an important role in the progression of coronary artery lesions <50%S. Improved therapeutic regimens to alter progression of atherosclerosis may require adjunctive therapy, such as with antioxidants or hormone replacement therapy, in concert with low-density lipoprotein cholesterol reduction to prevent new lesion formation or early lesion progression. Sequential coronary angiographic determination of progression evaluated by both quantitative coronary angiography and global change score, a visual assessment of overall lesion change, predicts clinical coronary events. Only inferences about the state of the arterial wall can be made from angiography, because it delineates only the lumen. Therapy testing and study of atherosclerosis progression can be improved with noninvasive B-mode ultrasonographic imaging of the distal common carotid artery far-wall intima-media thickness (IMT), a reliable measure of early preintrusive atherosclerosis. Measurement of common carotid IMT is useful for the study of coronary artery risk factors and can augment studies of coronary artery intrusive lesions, because it is associated with coronary artery disease. B-mode measurement of common carotid IMT has the potential of serving as a noninvasive surrogate end point for clinical coronary events. Screening for peripheral vessel changes indicative of high risk for coronary artery disease is possible and cost-effective with the noninvasive procedures now available. (Arterioscler Thromb. 1994;14:177-192.) Key Words • atherosclerosis • angiography • ultrasound • regression • clinical trials • intima-media thickness • quantitative computerized angiography • common carotid artery • coronary arteries • meta-analysis E vidence that progression of atherosclerosis can be retarded and atherosclerotic lesions can regress derives from several sources. These sources include studies of arterial lesions obtained at autopsy from starved human populations, animal experimentation, and clinical trials using serial angiography. In the first half of this article, we review serial angiographic evidence for atherosclerotic lesion improvement induced by diverse modes of int...