The distal anastomoses of thrombosed saphenous vein (11), bovine (4), Dacron (7), and polytetrafluoroethylene (PTFE) (27) grafts removed en bloc during reoperation or amputation were studied with light microscopy, scanning electron microscopy, and transmission electron microscopy. Analysis of the ultrastructures of the distal anastomostic regions was done to characterize morphogenesis of intimal hyperplasia and neointimal proliferation. Complete reendothelialization occurred in all vein grafts. In bovine heterografts, there were isolated areas of endothelia. Thrombosed PTFE grafts were lined with gelatinous, proteinaceous material with no consistent organized cellular pattern. In contrast, laminated fibrous tissue produced by fibroblasts lined the Dacron grafts. Intimal hyperplasia was found in 6 of 11 vein grafts and in all prosthetic grafts examined. Regardless of the type of graft used, intimal hyperplasia was found predominantly at the heel of the graft and on the floor of the artery. Beneath the endothelia, collagenous ground substance and myofibroblasts mixed with smooth muscle cells were seen, characterized by pyknotic nuclei, reduced cytoplasm/nuclei ratio, and loss of cytoplasmic organelles. Endothelialization occurred exclusively in vein grafts. Prosthetic grafts lacked endothelia, with the neointima consisting of fibroblasts and fibrous matrix. In intimal hyperplasia, two forms of smooth muscle cell pathomorphogenesis were recognized. Formation of myofibroblasts induced medial fibroplasia, whereas degeneration of muscle cells progressed to medial necrosis. Smooth muscle cells seem to play a role not previously recognized in the pathogenesis of graft failure.