In earlier studies, we have shown that porous (60 micron internodal distance) PTFE grafts develop a complete endothelial layer 2 weeks after being implanted in baboons. Subsequently, the intima of the graft thickens on account of SMC proliferation only where an overlying endothelial layer is present. SMCs in normal endothelialized artery proximal and distal to the graft show no detectable proliferation. The purpose of this study was to investigate the possibility that growth factors released from the graft endothelium or SMCs regulate SMC proliferation. PTFE grafts (4 mm I.D., 60 micron internodal distance) were placed in the aortoiliac circulation of baboons and removed at 2 weeks. The grafts were perfused ex vivo with tissue culture medium (Ham's F12 + 25 mmol/L HEPES and 2% calf plasma-derived serum) at 2.5 ml/hr for 5 hours. Perfused native carotid, aorta, and femoral arteries served as controls. After this period of perfusion, graft and arterial endothelium was intact as shown by scanning electron microscopy. The mitogenic activity (thymidine incorporation) of the perfusates was measured in an assay with quiescent 3T3 cells and baboon aortic SMCs and corrected for the surface area of the perfused vessels. These studies demonstrated markedly increased mitogenic activity in the perfusates of grafts compared with perfusates of native vessels. These results provide support for the hypothesis that the vascular wall cells in healing grafts can produce factors that regulate smooth muscle cell growth.