Failure to visualize the cystic duct and gallbladder during endoscopic retrograde cholangiography, while obtaining satisfactory opacification of the rest of the biliary system, is a radiographic sign of undetermined meaning. The diagnostic implication of this finding was analyzed in 63 patients with pathologically proven diagnoses. One patient was normal at surgery. Three groups of abnormal patients had: obstructing lesions of the distal common bile duct (35 patients); primary lesions of the cystic duct or gallbladder (19 patients); or obstructing lesions about the common hepatic/cystic duct junction (8 patients). The results indicate that obstructing lesions of the common bile duct may cause stasis of bile within the biliary system, increased biliary pressure, and sludge formation that prevent the flow of contrast material through the cystic duct and into the gallbladder, which can cause nonopacification. If the extrahepatic biliary system is of normal caliber without evidence of an obstructing process, nonfilling of the cystic duct and gallbladder is highly predictive of pathology.