The saphenous vein (SV) is the most commonly used conduit for coronary artery bypass surgery. However, using traditional techniques, the occlusion rate for the SV is high, with over 50% of grafts failing within 10 years. In conventional coronary artery bypass surgery the SV is exposed to considerable damage during preparation for grafting. Recently, an increased graft patency has been described using a 'no-touch' technique, whereby the vein is prepared with minimal vascular trauma. There is evidence that the success of this form of coronary artery bypass surgery is a result, at least in part, of the retention of tissue-derived nitric oxide. We have examined the effects of conventional SV harvesting on vessel morphology, cell proliferation, endothelin-1 and its receptors. Considerable damage was observed in veins prepared using conventional surgery compared to 'no-touch' veins. The vessel wall exhibited evidence of surgical trauma, with regions of denudation of the luminal endothelium caused by distension. Endothelin-1 and endothelin-A receptors were present at subintimal regions of conventional SV segments where proliferating cells were identified. Endothelial endothelin-B receptors were also revealed that were absent at areas of distension-induced damage to the endothelium. These results suggest that endothelin-1 plays a role in vein graft failure, predominantly via the endothelin-A receptor.