Objectives: To report quantitatively on the three-dimensional layered organization of the collagen and smooth muscle component of the two most successful vessels for coronary bypass-the internal mammary artery (IMA) and the long saphenous vein (SV). Our aim was to provide an explanation for the differential structural stiffness of these two vessels (both functioning at arterial pressures in their new environment), and how they might be susceptible to endothelial thickening. Methods: Eleven human saphenous veins and 23 internal mammary arteries were fixed at arterial distending pressure of 110 mmHg, and were sectioned in cross-section at 7 mu m thickness. A subset of these was also sectioned tangentially. Measurements of the three-dimensional alignment of collagen and smooth muscle fibers within the vessel wall were made using polarized light microscopy and the universal stage attachment. Data were plotted and analysed using circular statistics. Results: The IMA, structured like an elastic artery, is dominated by a media with discrete lamellae of wavy collagen and smooth muscle, aligned nearly circumferentially, with a low variability of alignment (mean circular SD 12 degrees). The SV is more variable in its size and structure, characteristically with a narrow circumferential media comprised mostly of collagen which is straightened and highly aligned at arterial pressures (mean circular SD 9 degrees). Circumferential collagen in the vein was often adjacent to longitudinal bundles of smooth muscle and collagen. Conclusions: The strikingly aligned structure of the SV complements the known high mechanical stiffness of this vessel when at arterial distending pressure. The high fraction of longitudinal muscle, in addition to the circumferential muscle cells in the SV make it vulnerable to any pre-implant surgical preparation, and to the cyclical luminal pressures and longitudinal strains characteristic for epicardial arteries.