Autogenous saphenous vein and synthetic materials, such as Dacron and expanded polytetrafluoroethylene, have been used extensively as vascular grafts with moderate success. Improved success rates for vascular graft surgery may be possible if superior graft material was available. We tested the use of autogenous small intestinal submucosa (SIS) as a large diameter (10 mm) vascular graft in the infrarenal aorta of 12 dogs. One dog died with graft thrombosis within 48 hr of surgery. Nine dogs were sacrificed at various times during a 52-week postsurgical period and showed patent grafts without infection, thrombosis, intimal hyperplasia, or adverse effects upon blood pressure. There was no ultrastructural evidence of endothelial cell growth on the luminal surface of the SIS graft which was composed of a dense, nonthrombogenic, organized collagenous connective tissue. The SIS material was approximately one order of magnitude less elastic than natural aorta and showed an immediate dilatation of approximately 18% after exposure to the systemic blood pressure. However, there was no progressive dilatation during the 52-week postsurgical period. Two dogs remain alive at 8 and 52 weeks postsurgery with patent grafts as determined by positive contrast radiography and Doppler studies. We conclude that autogenous small intestinal submucosa can be successfully used as a large diameter arterial graft in the dog and is worthy of further investigation.