Aim: To evaluate the function of the biliary sphincter 15 to 17 years after endoscopic sphincterotomy and to investigate if loss of sphincter function is associated with bacterial colonization, changes in bile composition, or inflammation of the biliary system. Methods: Eight patients who had undergone endoscopic sphincterotomy for bile duct stones 15 to 17 years previously underwent ERCP with biliary manometry, bile sampling, and biopsy. Manometry was performed using a perfused triple-lumen manometry catheter and a station pull-through technique. Bile samples were cultured and analyzed for biliary lipids, bile salts, bacterial β-glucuronidase, and phospholipase A₂. Biopsy specimens were taken from the proximal common hepatic duct for histologic examination. Results: Manometry demonstrated absent basal sphincter pressure and no choledochoduodenal pressure gradient in all patients. Phasic contractions were observed in two patients. Cholangiography showed stones in one patient. Positive cultures were obtained in three patients, including the patient with stones. All bile samples showed a high content of biliary lipids and cholesterol. Some samples contained considerable amounts of hydrophobic bile salts. Five samples contained very high levels of phospholipase A₂ activity. Significant bacterial β-glucuronidase activity was found in one patient, the patient with stones. Biopsy specimens of the proximal common hepatic duct in three patients showed chronic inflammation with fibrosis and reactive epithelial changes. Conclusions: After endoscopic sphincterotomy for bile duct stones, the function of the biliary sphincter is permanently lost. This is associated with bacterial colonization, presence of cytotoxic components in the bile, and chronic inflammation of the biliary system. (Gastronintest Endosc 1997;45:400-5.)