A total of 96 patients with gallbladder carcinoma in whom direct cholangiography clearly opacified the pancreaticobiliary ductal union and the common channel, and 65 patients with an anomalous union of these two duct systems at a distance greater than 15 mm from the papilla of Vater (normally less than 4.6 +/- 2.2 mm, mean +/- SD) were studied. It was found that this anomalous ductal union occurred in 16.7% of the patients with gallbladder carcinoma in comparison with an incidence of 2.8% among 641 consecutive patients with various hepatobiliary and pancreatic diseases studied by endoscopic retrograde cholangiopancreatography who did not have gallbladder carcinoma. It was also found that gallbladder carcinoma occurred in 24.6% of the 65 cases of anomalous ductal union in comparison with a 1.9% incidence of this cancer among 635 consecutive patients similarly studied and found to have normal ductal union (p less than 0.001). Thus, a close etiologic association was suggested between this anomaly in the terminal segment of the biliary tract and gallbladder carcinoma. Of the 65 patients with anomalous ductal union, 50 had the so-called congenital cystic dilatation of the common bile duct and 15 did not. Five of the 50 (10%) and 11 of the 15 (73.3%) had gallbladder carcinoma (p less than 0.01), and this carcinoma seems to be related to anomalous ductal union rather than to cystic dilatation of the common bile duct. As a tumorigenic factor in this anomaly, regurgitation of pancreatic juice has been stressed.