The pancreas of four patients with chronic hypergastrinemia and recurrent peptic ulcer--without pancreatic tumors--were studied by light and electron microscopy. Centroacinar and ductular cells were increased in number, enlarged and richer in organelles, microfilaments and apical microvilli compared to the controls. The hyperplasia of these cells was significantly correlated with the peak values of gastrinemia stimulated either by secretin or by calcium. Zymogenic cells were degranulated to various degrees and always had well-developed ergastoplasm and Golgi apparatus. The degree of degranulation was significantly correlated with the peak values of stimulated gastrinemia. Cells with features intermediate between ductular and islet cells were found near some islets and typical islet cells (mostly A and B cells) were observed in the walls of some ductules and acini. These results suggest enhanced secretion of both bicarbonate and enzymes and neogenesis of islet cells from ductular cells during chronic hypergastrinemia.