A new morphometric technique using image analysis has been developed to express the topographic distribution of atherosclerotic lesions in unambiguous statistical terms. Computer-stored images of opened Sudan IV-stained aortas and iliac and coronary arteries from hypercholesterolemic minipigs (n = 39) were used in this study. The image processing methods included transformation of the data to standard templates, automated image segmentation, and creation of probability-of-occurrence maps. These maps have shown that sudanophilic lesions are localized with a characteristic topography along the aortas and iliac and coronary arteries. Areas of high probability are associated with the entrance regions of vessels and the lateral leading edges of the major flow dividers. Regions immediately distal to large branches were found to be areas of low probability. Despite the association of areas of sudanophilia with entrance regions and branch points, a major portion of sudanophilic lesions was not associated with any orifice region (e.g., ductus scar, dorsolateral surface of abdominal aorta, and ventral surface of terminal aorta). The present study provides the necessary information for the development of a rational sampling strategy for the experimental study of the distribution of localizing factors (e.g., hemodynamic, biochemical, cellular, mass transport, histological) and their relationships to putative atherogenic mechanisms.