Our previous work on the effect of modification of peptide bonds in gastrin-like peptides led us to speculate that cleavage of the bond between the Met and Asp residues occurs in gastric mucosal membranes, and that this cleavage may have functional significance. In agreement with this speculation, we now show that the tetragastrin analogue BOC-Trp-Leu-Asp-Phe-NH2 (1) is degraded by a membrane fraction from rat gastric mucosa, and that the main products are BOC-Trp-Leu and Asp-Phe-NH2. Pseudo-peptide analogues in which the peptide bonds are replaced by CH2NH had differing stabilities; BOC-Trp-Leu-Asp-psi (CH2NH)-Phe NH2 (4) and BOC-Trp-Leu-psi(CH2NH)-Asp-Phe-NH2 (3) were stable under the incubation conditions, whereas BOC-Trp-psi(CH2NH)-Leu-Asp-Phe-NH2 (2) was degraded. The peptide and pseudo-peptide which were degraded (1 and 2) have been shown to stimulate gastric acid secretion in rats, in vivo, whereas 3 and 4 (which were not hydrolyzed) were inactive in stimulating gastric acid secretion and were found to antagonize the action of gastrin.