The purpose of this study was to examine whether an intermediate form of amidated gastrin, glycine-extended gastrin (Gly-G), can stimulate gastric acid secretion in conscious rats prepared with gastric fistulas. Intravenous administration of Gly-G (20 nmol.kg-1.h-1) alone for 2 h did not stimulate gastric acid secretion; however, administration of Gly-G (20 nmol.kg-1.h-1) in combination with a bolus administration of gastrin (9.5 nmol/kg) potentiated acid secretion significantly. Gastric acid secretion in response to gastrin alone and gastrin plus Gly-G (2 nmol.kg-1.h-1) was 109.1 +/- 21.6 and 170.1 +/- 27.7 mueq.kg-1.h-1, respectively (P < 0.05). Gastric acid secretion in response to gastrin alone and gastrin plus Gly-G (20 nmol.kg-1.h-1) was 84.8 +/- 17.5 and 164.1 +/- 29.3 mueq.kg-1.h-1, respectively (P < 0.05). Intravenous administration of Gly-G (20 nmol.kg-1.h-1) failed to increase histamine (1 mg/kg)-stimulated acid output. These results demonstrate that Gly-G can selectively potentiate the stimulatory effect of gastrin on acid secretion in rats and that the unprocessed form of gastrin, Gly-G, can exert a biological effect in the stomach.