The effect of a commercially available mixed amino acids solution, when given either intravenously or intragastrically, on lower esophageal sphincter (LES) pressure, frequency of transient LES relaxations (TLESRs) and gastroesophageal reflux (GER) was investigated in six healthy volunteers. LES pressure and esophageal pH were simultaneously recorded on three separate occasions 1 hr before (basal) and 3 hr during intravenous or intragastric infusion of amino acids (250 mg protein/kg/hr) or saline (control). No significant changes in LES pressure were seen in the control experiment. Intravenous amino acids caused a rapid and sustained (P < 0.01) decrease in LES pressure whereas intragastric amino acids decreased LES pressure only gradually and temporarily (P < 0.01). In the three experiments no significant differences were observed in TLESR frequency, the number of GER episodes, the mechanism of reflux, or duration of acid exposure. In healthy subjects both intragastric and, especially, intravenous infusion of amino acids significantly decrease LES pressure but do not affect the frequency of TLESRs or GER episodes during a continuous liquid gastric load.