BACKGROUND: The gamma-aminobutyric acid receptor type B agonist, baclofen, inhibits transient lower oesophageal sphincter relaxations by influencing a vagal pathway. Although post-prandial proximal gastric function, which is vagally mediated, is important in the occurrence of transient lower oesophageal sphincter relaxations, the effects of baclofen on post-prandial proximal gastric motility in humans remains undetermined. AIM: To determine the effects of baclofen on post-prandial lower oesophageal sphincter function and proximal gastric motility in healthy subjects. METHODS: In 11 healthy volunteers, a barostat bag and an oesophageal manometric catheter with a sleeve were simultaneously positioned; 40 mg of oral baclofen or placebo was then given in a randomized, double-blind manner. Subsequently, the intragastric bag volume, oesophageal and lower oesophageal sphincter pressure and oesophageal pH were recorded during the 90 min before and 120 min after a meal. RESULTS: During the post-prandial period, unlike the fasting period, baclofen decreased the rate of transient lower oesophageal sphincter relaxations and increased the basal lower oesophageal sphincter pressure compared with placebo. However, the meal-induced decrease in the tone and phasic contractility of the fundus was not affected by baclofen. CONCLUSION: The gamma-aminobutyric acid receptor type B agonist, baclofen, has a potent effect on post-prandial lower oesophageal sphincter motility without altering post-prandial proximal gastric motility, suggesting differential effects of baclofen on different signals of gastrointestinal vagal afferents.