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In a prospective study of 112 patients suspected of periampullary cancer endoscopic retrograde cholangiopancreatography (ERCP) was successfully performed in 87 patients (78%). Technical failures were due to gastric outlet obstruction in four patients and inability to cannulate the ampulla of Vater in 21 patients. Successfully performed ERCP had both a high sensitivity (92%) and specificity (90%) for periampullary cancer. The few errors in pancreatogram interpretation were due to juxta-ductal cancers and difficulty in differentiating duct changes of cancer from those of chronic pancreatitis. Pancreatic cytology, performed in 21 patients, was reliable, diagnosed two pancreatic cancers when the pancreatogram failed and, if used routinely, assists interpretation of the pancreatogram. Retrograde cholangiography provided a correct diagnosis in six jaundiced patients with normal pancreatograms. Three complications of ERCP occurred in this series.