BACKGROUND Cholangiocarcinoma develops in 5% to 15% of patients with choledochal cysts, sclerosing cholangitis, and intrahepatic stones. The detection of cholangiocarcinoma in patients with premalignant biliary conditions has been difficult. Serum levels of carcinoembryonic antigen (CEA) have been neither sensitive nor specific for the diagnosis of cholangiocarcinoma. However, CEA has been shown to be present in cholangiocarcinomas by immunohistochemical staining. Therefore, we measured the level of CEA excreted in bile in patients with benign strictures, premalignant biliary diseases, and cholangiocarcinoma. METHODS Bile was obtained from transhepatic stents in patients with benign biliary strictures (34), choledochal cysts (5), primary sclerosing cholangitis (6), intrahepatic cholelithiasis (5), and perihilar cholangiocarcinoma (25). Samples were analyzed for CEA using a solid phase, two-site immunoenzymetric assay. RESULTS Biliary CEA levels were significantly elevated (P < 0.01) in patients with cholangiocarcinoma (50.2 +/- 5.8 ng/mL) and intrahepatic cholelithiasis (57.4 +/- 10.4 ng/mL) compared with patients with benign strictures (10.1 +/- 3.9 ng/mL). Patients with sclerosing cholangitis (21.6 +/- 3.9 ng/mL) and choledochal cysts (20.0 +/- 16.5 ng/mL) had intermediate levels. In 5 patients undergoing resection of perihilar cholangiocarcinomas, the mean biliary CEA level decreased from a preoperative level of 46.8 +/- 6.7 ng/mL to a postoperative level of 11.3 +/- 5.6 ng/mL (P < 0.02). In 4 patients with progression of cholangiocarcinoma, biliary CEA increased from a mean of 53.3 +/- 6.9 ng/mL to 98.3 +/- 12.2 ng/mL (P < 0.02) over a mean interval of 9.5 months. CONCLUSIONS Increased levels of CEA can be detected in the bile of patients with chlolangiocarcinoma. Monitoring these levels may have a role in the management of cholangiocarcinoma as well as premalignant biliary conditions such as choledochal cysts and sclerosing cholangitis.