There is considerable evidence that opioid mechanisms are involved in the mediation of pyloric motor responses that in turn regulate gastric emptying. The purpose of this randomized, placebo-controlled crossover study was to investigate the effect of naloxone on gastric emptying of a solid meal, gastric myoelectrical activity and the postprandial release of gastrointestinal peptides and neuropeptides in 20 healthy volunteers. Naloxone was administered as an intravenous bolus, followed by continuous infusion according to an intravenous dosing nomogram. Gastric emptying time was evaluated by scintigraphy and gastric myoelectrical activity was evaluated by cutaneous electrogastrography. Naloxone did not significantly alter gastric half-emptying time and postprandial dominant gastric electrical frequency compared with placebo. It also did not significantly change the plasma levels of several peptide hormones with the exception of neuropeptide Y, which was significantly increased (P = 0.001). In conclusion, in doses that influence human intestinal motility, naloxone had no effect on gastric motility and release of several peptide hormones in healthy male volunteers. The importance of the isolated increased neuropeptide Y plasma level needs further investigation.