Gastric distension is a potent stimulus of transient lower esophageal sphincter (LES) relaxation. In order to investigate the time effect of prolonged gastric distension on the rate of transient LES relaxations, LES pressure, and the motor and sensory function of the proximal stomach, we performed a continuous isobaric distension of the proximal stomach at the 75% threshold pressure for discomfort for 2 hours in seven healthy subjects. A multilumen assembly incorporating a sleeve and an electronic barostat were used. The rate of transient LES relaxations (n/30 min) was constant during the first hour [4.1±1.2 (0-30 min) and 5.4±1.1 (30-60 min)], but markedly decreased (p<0.05) in the second hour [2.1±0.5 (60-90 min) and 2.3±0.9 (90-120 min)], whereas LES pressure, baseline volume and volume waves within the gastric bag, hunger and fullness did not change throughout the experiment. It is concluded that the rate of transient LES relaxations decreases with time during prolonged gastric distension, thus suggesting that this type of stimulus should not be used in sequential experimental conditions.