The effect of endogenously released pancreatic glucagon on pentagastrin-stimulated lower esophageal sphincter pressure (LES-P) was studied in 10 healthy subjects. Glucagon was released by continuous intravenous infusion of 1-arginine in a dose of 0.6 g/kg-h, which resulted in plasma concentrations of pancreatic glucagon comparable to those seen after a protein meal. Infusion of arginine resulted in a significant inhibition of pentagastrin (0.5 mug/kg-h) stimulated LES-P. Five of the subjects furthermore had a study of the effect of exogenous glucagon in a dose of 1.6 mjg/kg-h on pentagastrin-stimulated LES-P. This dose of glucagon also reduced LES-P, but in spite of higher plasma glucagon concentrations, to a lesser degree than arginine.