Autogenous vein grafts used for canine femoral and aortocoronary arterial bypasses were evaluated from 2 to 365 days postoperatively. Femoral grafts showed focal endothelial disruption, mural fibrin deposition, and medial edema with inflammatory infiltrates during the first week; loss of medial smooth muscle cells and focal subendothelial lesions with intact endothelium by 2 weeks; and diffuse subendothelial lesions by 12 weeks, Coronary grafts studied at 6, 9, and 12 months had medial fibrosis and extensive intimal proliferation causing up to 90% luminal narrowing. Extension of the intimal process into the coronary artery distal to the bypass graft also compromised the arterial lumen. Coronary grafts obtained from humans dying 17 and 57 days after graft insertion revealed a similar subendothelial proliferation. Electron microscopy showed that the subendothelial lesions were composed of mature smooth muscle cells and collagen primarily oriented parallel to the axis of blood flow. Recurrent endothelial cell damage, followed by mural fibrin deposition and organization, appears to be the cause of the subendothelial proliferative lesions.