Specimens from the lower esophageal sphincter (LES) region of the pig were analyzed for galanin-like immunoreactivity (GAL-LI) using radioimmunoassay and immunohistochemistry. The mean concentration of GAL-LI was 3.4 pmol/g tissue. GAL-LI nerve fibers were observed surrounding muscle bundles in the smooth circular muscle layer, and in ganglion cells of the myenteric plexus. Bolus injection of 40-200 pmol/kg of galanin directly into the arterial supply of the resting LES increased the LES pressure (LESP) dose-dependently, whereas slow infusion of 2-100 pmol galanin/kg/min had no effect on resting LESP. The vagally increased LESP was not modulated by simultaneous galanin infusion, and the concentration of galanin in the venous effluent of the LES declined insignificantly during vagal stimulation. It is concluded that galanin may be an important neuropeptide for the modulation of resting LES tone.