Although older work indicated that luminal peptides are stimulants of pancreatic secretion, these earlier experiments were performed with crude peptide mixtures containing amino acids that are also known stimulants. Furthermore, no information was provided about size or composition of stimulating peptides. For this reason, the problem was reinvestigated with commercially synthesized oligopeptides in dogs equipped with chronic gastric and pancreatic fistulas. Synthetic peptides at 30 mM concentrations were perfused into the proximal bowel when luminal pancreatic proteases were reduced to undetectable concentrations and dogs were receiving intravenous exogenous secretin infusions. Increases in pancreatic outputs of protein and bicarbonate were measured. Of the peptides tested, only glycylphenylalanine, glycyltryptophan, and phenylalanylglycine stimulated, whereas both di- and triglycine were without effect. It was concluded that some, but not all, oligopeptides in the gut lumen are stimulants of pancreatic secretion.