Progress in vascular surgery has been owing to the development of vascular prosthesis. However, clinical results of small-caliber synthetic vascular prostheses, which were applied to coronary surgery and infrainguinal arterial reconstruction, have been still inferior to those of autogenous vein graft. Since Maruyama succeeded in culturing vascular endothelial cells from human umbilical cord vein in 1963, tissue culture of vascular endothelium has played an important role of clarifying various aspects of thrombosis, fibrinolysis and atherosclerosis. In order to improve the patency rate of small-caliber vascular graft, the idea to connect tissue culture with synthetic material was occurred to mind. Since 1978 endothelial cell seeding has been investigated for the purpose to provide native antithrombogenicity to synthetic vascular prosthesis. There were many reports about the better patency, the earlier endothelialization and the less platelet adhesion on the luminal surface of the experimentally seeded graft. Recently “prelined graft”, which is made from in vitro seeding of cultured endothelial cells, has been paid attention to rather than the classical technique of endothelial seeding with preclotting method. In our bioresearch laboratory vascular endothelial cells were derived enzymatically from canine external jugular veins. They were cultured to confluency and seeded in vitro to small-caliber vascular prostheses by the rotation method. Experimental results of animal implantation in 8 weeks revealed that the endothelial seeded graft had superior patency to control graft. Seeded endothelial cells were observed histologically to form monolayer lining at the middle portion on the inner surface. Their function was confirmed by the peroxidase antiperoxidase reaction to identify Factor VIII related antigen in the cell body. Subendothelial structure was examined thinner in the intimal area of good endothelial coverage. There are several problems about hybrid vascular prosthesis, which is concomitantly composed of synthetic material and cultured vascular cells. First, experienced technique of tissue culture should be mastered for harvesting cells and maintenance of the experimental graft. Study of vascular smooth muscle cell and extracellular matrix should be also advanced in pararell with that of endothelial cells. Synthetic material should be searched in pursuit of biodegradable or bioresorbable graft which is expected to have cell affinity. Concerning the cell attachment, necessity of coating substance on the graft such as adhesive protein should be reconsidered. Seeded endothelial cells should be evaluated from the immunological point of view before clinical application, because cultured cells from human vascular wall may acquire various antigenicity in the course of tissue culture. Seeding of cultured endothelial cells in vitro will be an evolutionary trend for the development of small-caliber synthetic vascular prosthesis.