To investigate the effect of oligopeptides on gastric secretion in humans, we investigated acid secretion in healthy volunteers after the intragastric infusion of physiological saline, glycine (100 mM), diglycine (50 mM), triglycine (33 mM), and tetraglycine (25 mM). All test solutions were equivalent in glycine content, osmolality (300 mosmol), and pH (5.5). Although the rate of acid secretion was greater during glycine than saline infusion [5.6 +/- 0.8 vs. 3.3 +/- 1.1 mmol/h (means +/- SE); P less than 0.05], the rate of acid secretion during glycine infusion was not significantly different from that induced by its related peptides. There were increases in plasma glycine concentration during infusion of glycine and its related peptides but no detectable changes in serum gastrin levels. The increases in plasma glycine must have been due to absorption from the small intestine because there was no gastric absorption of glycine in free or dipeptide form nor diglycine hydrolysis in the stomach. Therefore, our results permit implicating only the increased plasma glycine concentrations as the stimulus for acid secretion by glycine and its homologous peptides.