Intravascular ultrasound provides cross-sectional images of arteries and enables accurate delineation of lumen dimensions and wall structure. Moreover, ultrasound characterization of atherosclerotic plaque subtypes may have important implications in determining the natural history and the clinical outcome of patients with coronary artery disease. The reliability of intravascular ultrasound to differentiate plaque morphology subtypes was studied in 60 coronary segments excised from 33 coronary arteries obtained from 17 patients at necropsy. Ultrasound was performed with a 25-MHz transducer mounted on the distal end of a rigid probe that was rotated manually inside the lumen artery. Plane film radiography was also performed to establish the presence of calcific deposits. A total of 82 histologic transverse sections corresponding to 82 ultrasound imaging sites were studied from the 60 coronary segments. Of the first 54 images, 36 were fibrous plaques and yielded dense homogenous echo reflections, 6 had discrete areas of lipid that were less echogenic and 12 had calcific deposits that cast echo-free shadows beyond areas of intense echo reflections. The predictive accuracy of evaluating plaque composition in the remaining 28 ultrasound imaging sites was 96%. Thus, anatomical structure of coronary arteries and composition of atherosclerotic lesions can be assessed accurately with intravascular ultrasound and may have potential for better understanding of the atherosclerotic process and provide guidance to interventional procedures.