Expression of tenascin, type IV collagen and laminin during human intrahepatic bile duct development and in cholangiocarcinoma was examined by immunohistochemistry. In the developing hilar bile ducts, tenascin was expressed in the mesenchyme around the epithelial cells migrating from the ductal plate into the mesenchyme at 10-14 weeks of gestation. Tenascin was also expressed in the mesenchyme around newly formed hilar bile ducts at 15-20 weeks of gestation, but its expression disappeared after 21 weeks of gestation. Type IV collagen and laminin were expressed around the ductal plate, around epithelial cells migrating from the ductal plate into the mesenchyme, and around newly formed hilar bile ducts, and their expression was present throughout fetal life. By contrast, in the development of peripheral bile ducts, tenascin expression was not found. Type IV collagen and laminin were identified around the ductal plate, migrating epithelial cells and peripheral bile ducts. In cholangiocarcinoma, tenascin and type IV collagen were expressed in the stroma, but laminin was not identified. These findings suggest that tenascin may play a role in hilar bile duct development and that type IV collagen and laminin may play a role in both hilar and peripheral bile duct development. Expression of tenascin and type IV collagen in the stroma of cholangiocarcinoma may be the result of malignant transformation of intrahepatic biliary epithelium; tenascin in peritumoral stroma may stimulate carcinoma cell proliferation and growth in cholangiocarcinoma.