Over a five-year period, we measured concentrations of gut hormones in plasma samples from 353 patients in whom diagnoses of pancreatic endocrine tumors were subsequently confirmed. A median of 19 months (range, 7 to 120) after the initial diagnosis, 24 of these patients (6.8 percent) had elevated concentrations of other hormones in association with new clinical symptoms. In 13 of these patients (8 with glucagonomas, 3 with tumors secreting vasoactive intestinal polypeptide, and 2 with insulinomas), hypergastrinemia developed along with the clinical features of a gastrinoma; 5 patients died of gastrointestinal perforation or bleeding, apparently caused by this second tumor. We conclude that patients with pancreatic endocrine tumors, regardless of their initial clinical picture, require continued surveillance for new elevations of hormones.