Malignant obstruction of the pancreaticobiliary system is a frequent indication for ERCP. Twenty-five patients with abnormalities suggestive of malignancy were encountered during ERCP at our institution and brush cytology was obtained. Positive cytology specimens were collected in 12 of 20 (60%) cases of malignancy causing biliary obstruction. Using a recently developed cytology brush for the biliary tree, detection of malignancy in strictures of the bile duct had a sensitivity of 50% and a specificity of 100%. Both cases of cholangiocarcinoma were diagnosed with cytology, as were 5 of 10 cases of pancreatic cancer. It is concluded that brush cytology is a diagnostically reliable, highly specific technique for malignant lesions encountered at ERCP. In experienced hands, a positive cytologic result may obviate the need for additional invasive diagnostic studies.