OBJECTIVE Genetically-modified mice are the preferred model for studies on atherogenesis. Conventional procedures for determining lesion size and composition may be not very accurate, especially when only very small lesions are present. We provide here a detailed characterization of lesion components and the computer-assisted quantitative determination of atherogenesis in apolipoprotein E-knockout (apoE-/-) mice. RESULTS Atherosclerotic lesions were detected at typical predilection sites in the aorta: the small curvature of the arch, the orifices of the brachiocephalic trunk, the left subclavia and common carotid artery, the branch sites of the mesenteric and renal arteries, the abdominal aorta, and the iliac bifurcation. We found that these lesions covered 20% of the aortic surface of apoE-/- on average compared with 1% of the wild type C57BL/6 mice (p < 0.00001). As expected, immunocytochemistry revealed "oxidation-specific" epitopes, i.e. epitopes generated during the oxidation of LDL and other lipoproteins, in aorta from apoE-/- mice. CONCLUSIONS Although some limitations may reduce the applicability of results obtained in mice to humans, the apoE-/- mouse appears to be suitable for investigation of the role of apolipoproteins, enzymes and receptors involved in lipid metabolism, lipid oxidation, vascular cells and their secretory products as well as the possible role of antioxidants and gene-therapy in reducing atherogenesis.