Oxyntomodulin (OXM), a 37-amino acid glucagon-containing peptide produced mainly in intestine and endocrine pancreas, is present in rat plasma and inhibits pentagastrin-stimulated gastric acid secretion in both the anesthetized and the conscious rat. In order to investigate the modifications in acid and water secretions in a physiological model, we set up a protocol which allowed us to study acid secretion in the conscious rat both under basal conditions (during an 18-hour fast) or after a physiological stimulus (a liquid meal). OXM (110 pmol X kg-1) did not modify the basal acid or water output in an 18-hour fasting state. When injected before the test meal, OXM (225 pmol X kg-1) sharply decreased the acid output stimulated by a liquid meal (milk), which represented 10 times the basal value. Results are compared to those obtained when pentagastrin was the stimulant. Synthetic C-terminal octapeptide of OXM was able to inhibit both basal and meal-stimulated secretions. We can conclude that OXM, or a closely related peptide containing the C-terminal octapeptide, may be a physiological regulator of gastric functions.