Tissue encapsulating Dacron® vascular prostheses recovered from humans were extracted and analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis to determine the distribution of genetically distinct collagen types. Type V collagen was in maximal concentration in extracts of tissues nearest to the prosthesis lumen. The pattern of distribution of collagen types across the prosthesis wall may be due to the influence of modulating factors originating in the blood flowing through the prosthesis, and factors produced by inflammatory cells chronically present at the tissue-biomaterial interface. We postulate that the macrophage may play a key role in determining the composition and organization of the pseudointima of human vascular grafts and the neointima in vascular grafts in animals. We suggest that the increased proportion of Type V collagen at or near the lumen contributes to the relatively nonthrombogenic properties of human pseudointima.