To detect cellular differences in the healing of polytetrafluoroethylene (e-PTFE) and Dacron grafts up to 7 months after implantation, we studied 108 aortic graft interpositions in dogs. Each prosthesis was alternately prepared by endothelial seeding or by an unseeded control method. The grafts were perfusion fixed and studied with light, scanning, and transmission electron microscopy at intervals from before to 221 days after implantation. Seeding resulted in the development of an extensive endothelial flow surface in two out of three of the e-PTFE and none out of four of the Dacron grafts by 10 days after implantation (p = 0.053). After 30 days a microfibrillar subendothelial matrix ranging from 5 to 11 mu formed in all but three grafts with endothelial coverage. The inner capsule of mature Dacron grafts was significantly thicker (169 +/- 143 mu) than in e-PTFE grafts (22 +/- 32 mu; p = 0.002). Seeded and unseeded Dacron grafts had predominantly fibroblasts in the outer capsule of the graft by 10 days. Surface endothelium, vasa vasorum, fibroblasts, and myointimal cells appeared in the inner capsule between 10 and 30 days after implantation. In Dacron grafts, fibroblasts and myointimal cells predominated in the inner capsule at 30 days, with smooth muscle cells not being definitely identifiable until after 150 days. Neither fibroblasts nor myointimal cells were common (present but sparse in one of four e-PTFE grafts) at 30 days, and transmural vasa vasorum were never seen. The seeded endothelial cells migrated rapidly from the sites of initial adhesion near the e-PTFE onto the flow surface. Only one of four of the unseeded e-PTFE grafts had surface endothelium after 30 days, and only moderate coverage developed during 180 days. We conclude that endothelial healing is more rapid in seeded e-PTFE grafts than in seeded Dacron grafts and occurs by a different mechanism.