A retrospective analysis of complications arising from 300 consecutive attempts at endoscopic retrograde cholangiopancreatography (ERCP) in 278 patients was undetaken to determine the rate and severity of complications. An over-all complication rate of 5% (15 cases) was documented. Complications were categorized in terms of those arising from endoscopy itself or from the administration of pharmacological agents (7 cases), and those observed after the injection of radioopaque contrast into the biliary tree or pancreas (8 cases). Complications which might be considered coincidental to a patient's underlying illness were not excluded. Complications were significantly more frequent after injection of diseased duct systems. Brief, self-limited pancreatitis after retrograde pancreatography occurred in 5 of 90 patients with pancreatic disease. No cases of pancreatitis were observed after retrograde pancreatography in 102 patients without pancreatic disease X2 = 5.82, P less than 0.025). Sepsis occurred after retrograde cholangiography in 3 of 56 patients with extrahepatic biliary obstruction. In the absence of extrahepatic obstruction, cholangiography was performed without complication in 85 cases (X2 = 3.62, P less than 0.1), although 25 of these had intense cholestasis due to hepatic parenchymal disease. This analysis provides the basis for modifications of ERCP technique and management that may reduce the future incidence of complications. This study suggests that the incidence and severity of complications that arise from ERCP compare favorably with procedures of equivalent diagnostic yield.