The exact mechanism that leads to thrombosis of small-diameter vascular prostheses (less than 4 mm X greater than 6 cm) is unknown. This report presents preliminary patency and healing data on a sequential detergent-extraction technique for the preparation of autogenous small-diameter microvascular grafts. Fifteen carotid interpositional allografts (3 to 4 mm X 4 to 6 cm) were implanted in 15 mixed species adult greyhounds. Ninety days after implantation grafts were perfusion-fixed in situ, harvested, and evaluated by light microscopy and scanning and transmission electron microscopy. Two categories of acellular vascular matrix grafts were evaluated: non-cross-linked and cross-linked (1% carbodiimide). By objective morphologic analysis with blind random view, histologic sections were rated from 0 to 4 in five categories believed to be important for graft healing and patency. Overall graft patency was 80% (12 of 15), and there was no significant difference between cross-linked and non-cross-linked grafts. Non-cross-linked grafts were superior to cross-linked grafts in all areas of histologic evaluation except immunogenicity (p less than 0.01). Most important, non-cross-linked grafts demonstrated complete endothelial coverage (p less than 0.001). There was no significant difference (that is, normal) between control autografts and non-cross-linked grafts; however, there was a significant difference between control autografts and cross-linked grafts in all parameters except immunogenic reaction (p less than 0.01).