The ability of the proglucagon-derived peptides oxyntomodulin and truncated glucagon-like peptide-1 (7-36)amide to stimulate somatostatin release from cultured rabbit fundic D-cells was assessed. Significant stimulation of somatostatin release was seen with both peptides at 10 nM. Potentiation of the stimulatory action of cholecystokinin was seen with both peptides at both 100 pM and 10 nM. The paracrine release of somatostatin from fundic D-cells may explain the acid inhibitory actions of the enteroglucagons. The different small bowel-derived peptides may interact at the level of the D-cell to regulate gastric acid secretion.