Background: We determined the accuracy of intraductal ultrasonography (IDUS) in distinguishing between bile duct cancer and benign bile duct disease. Methods: Patients (n = 42) who required bile duct biopsy using percutaneous transhepatic cholangioscopy (PTCS) to evaluate bile duct strictures or filling defects were studied. A thin-caliber ultrasonic probe (2.0 mm diameter and 20 MHz frequency) was inserted into the bile duct, and its images were prospectively reviewed before PTCS. Results: Disruption of the bile duct wall structure, seen on IDUS, was associated with malignancy in 25 of 26 patients. When IDUS demonstrated a lesion with normal bile duct structure, six of nine patients were found to have no malignancy. IDUS demonstrated no intraductal lesion in seven patients, and bile duct biopsy also did not indicate cancer in any of these patients. The accuracy, sensitivity, and specificity of IDUS for diagnosing bile duct cancer were 76%, 89%, and 50%, respectively. When used in tandem with IDUS, the sensitivity of bile cytology (64%) and PTCS (93%) improved to 96% and 100%, respectively. Conclusions: The accuracy of IDUS for diagnosing bile duct cancer was less than that of PTCS (95%). However, the sensitivity for bile cytology, or bile duct biopsy improved when performed in combination with IDUS. (Gastrointest Endosc 1998;47:341-9.)