Background and aims: Acupuncture has been shown to modulate visceral sensation and function. Traditionally, stimulation at the Neiguan (pericardial meridian) has been used to treat upper gastrointestinal symptoms. Some of the effects of acupuncture may be mediated through release of endogenous opioids and are reversed by naloxone. Gastric distension is the major trigger for transient lower esophageal sphincter relaxations (TLESRs). The aim of this study was to investigate the effect of electric stimulation at the Neiguan and naloxone on the TLESRs. Methods: In 14 healthy volunteers electrical acupoint stimulation was applied at the Neiguan and a sham point on the hip in a randomized order on the same day. In 12 healthy volunteers the effects of naloxone (80µg/kg intravenous bolus injection) and saline on electrical acupoint stimulation were compared on separate days at least 1 week apart. Esophageal motility was measured during distension of the proximal stomach with 500ml of air using barostat balloon. Results: Electric acupoint stimulation at the Neiguan decreased the rate of TLESRs by approximately 40% from a median of 6 per hour to 3.5 per hour (P<0.02). Acupoint stimulation had no effect on basal LES pressure, the residual LES pressure during TLESRs, the duration of TLESRs, or gastrointestinal symptoms of fullness, bloating, discomfort or nausea. The effect of acupoint stimulation was not inhibited by naloxone. Conclusions: Electric acupoint stimulation at the Neiguan significantly inhibits the frequency of TLESRs in response to gastric distention in healthy subjects. This effect does not appear to be mediated through µ-opioid receptors.