Purpose: The purpose of this study was to perform a preliminary histopathologic analysis of explanted human endovascular stented grafts from patients treated for occlusive disease. Methods: Over a 16-month period, 26 endovascular stented grafts were placed in 21 patients with limb-threatening ischemia caused by aortoiliac or femoral artery occlusive disease. All grafts were inserted through open arteriotomies remote from the region of primary disease. During the follow-up period, two patients died of preexisting heart disease 2 weeks and 7 months after grafting, and a portion of their endovascular grafts with the surrounding artery was explanted. Specimens from five other endovascular grafts were obtained during surgical revision for graft stenosis after 3 and 6 weeks and for outflow artery stenosis after 3, 5, and 6 months. All specimens were formalin fixed and studied with hematoxylin and eosin and trichrome staining and immunohistochemically for factor VIII-related antigen, alpha actin smooth muscle, macrophage antigen (MAC-387) and PC-10 (a mouse monoclonal antibody which specifically recognizes proliferating cell nuclear antigen in paraffin sections). Results: Three weeks after placement of the stented grafts, organizing thrombus was present on both surfaces of the expanded polytetrafluoroethylene (PTFE) grafts. At 6 weeks, evidence of a neointima with overlying endothelium was seen in the perianastomotic region, and 3 months after grafting it was seen 1 to 3 cm from the anastomosis. The specimen explanted at 5 months demonstrated factor VIII-positive cells 8 cm from the anastomosis. The histopathologic condition of the external capsule appeared to vary, depending on the presence or absence of an external wrap on the PTFE graft and on which layer in the arterial wall the graft was inserted. A foreign body reaction characterized by multinucleated giant cells was seen adjacent to wrapped grafts or around those placed in an intraadventitial plane. Grafts inserted within the media were surrounded by orderly, arranged, smooth muscle cells and few mononuclear cells. Extensive smooth muscle cell proliferation (PC-10 activity) was not seen within native artery atherosclerotic plaques peripherally displaced and external to prosthetic endovascular grafts. Conclusions: These preliminary observations on the healing of PTFE endovascular stented grafts in human beings demonstrate limited plaque hyperplasia and the presence of endothelial cells on the luminal surface remote from the graft-artery anastomosis. It is unclear whether this is a unique manifestation of healing in prosthetic grafts inserted within the walls of arteries. (J VASC SURG 1995;21:595-604.).