Despite the therapeutic success of coronary artery bypass grafting (CABG) using autologous saphenous vein, there is still a 50% failure rate within ten years after the procedure. Although the reasons why are not clear, vein grafts are associated with adventitial remodelling which may influence innervation of the graft, which in turn may influence graft thickening through the release of mitogenic neurtrotransmitters. Since little work has been done in this area, we investigated neural distribution in porcine vein grafts. In ungrafted saphenous veins abundant perivascular nerves were located in the outer region of the media with only few paravascular nerves in the adventitia. In vein grafts at one month after implantation, there was almost a complete depletion of perivascular nerves in the media. In contrast, in the neoadventitia, there was an emphatic appearance of large paravascular nerve bundles and a marked increase in small paravascular nerves. These changes were marginally more pronounced at six months after surgery, although the principal changes had occurred within one month. We also found that endothelin-1 and its receptors were closely associated with this neoinnervation of the grafts. These data indicate that neural reorganisation and ET-1 may play a role in the pathobiology of vein graft thickening, possibly through augmentation of vascular smooth muscle cell proliferation and migration. These data may be useful in devising novel therapeutic strategies aimed at reducing vein graft failure.