The present study investigated the pathogenesis of desmoplastic stroma formation, which is characteristic of most bile duct carcinomas and other scirrhous carcinomas. Using immunohistochemical analysis, the expression of collagen types I and IV, laminin and TGF-beta1 was examined in human extrahepatic bile duct carcinoma and compared with gastric and colon carcinoma. In addition to delineating the basement membranes of carcinoma nests and blood vessels, collagen type IV was present along the thick bundles of collagenous fibers in the stroma of extrahepatic bile duct carcinoma and scirrhous gastric carcinoma. The immunoreactivity of collagen type IV was strong in the adjacent or surrounding interstitium of tumor cell nests, but was absent or weak in older, more central portions of the tumor that contained sclerotic collagen. In situ hybridization demonstrated active expression of collagen alpha1(IV) mRNA in extrahepatic bile duct carcinoma and scirrhous gastric carcinoma cells. These results suggest that, although collagen type IV is typically a component of the basement membrane, it is expressed in the interstitial stroma of extrahepatic bile duct carcinoma and scirrhous gastric carcinoma where it may play a role in desmoplastic stroma formation.