Failure of infra-inguinal vein grafts appears to be due to the development of intrinsic lesions (intimal hyperplasia, fibrous stenoses) within the graft which lead to narrowing of the lumen, poor blood flow and thrombosis. The cause of these lesions remains unknown but recently it has been suggested that endothelial injury might be an aetiological factor. The damage that can occur after preparation of reversed vein grafts includes loss of endothelial cells and functional impairment of those cells that remain, in that the ability to produce prostacyclin and endothelium-derived relaxing factor (EDRF) is reduced. The preparation of in situ grafts is different to that for reversed grafts in that a valvulotome is passed along the lumen of the vein to destroy the valves. However, little is known about the degree of endothelial injury that this technique causes. Vein samples were obtained from patients undergoing infra-inguinal and coronary artery bypass grafting. The veins were mounted in an organ bath system to measure isometric tension and exposed to the endothelium-dependent agents acetylcholine, bradykinin, adenosine, histamine and the endothelium-independent agent sodium nitroprusside. The results indicate that preparation of reversed vein grafts leads to some loss of endothelial cells with functional impairment of the cells that remain. However, preparation of in situ grafts leads to severe or total loss of endothelial cells which resulted in an absence of detectable EDRF release. These findings were confirmed by histological examination of the vein samples.