We studied the effect of morphine and naloxone on lower esophageal sphincter pressure, esophageal contraction amplitude, and gastric emptying of solids and liquids in ten normal healthy subjects. Morphine sulfate in a dose of 8 mg intravenous bolus significantly decreased sphincter pressure with a maximum fall of 22.8% of the basal tone. Naloxone, 5 mg intravenous bolus, resulted in a 20% increase in the baseline pressure. There was no change in the esophageal contraction amplitude, duration, or frequency of peristalsis with either morphine or naloxone. Gastric emptying was measured using a dual-isotope technique to simultaneously assess the emptying rates of both solid and liquid meal components. Morphine, 8 mg intravenous bolus, led to a significant inhibition (P less than 0.05) of the gastric emptying of both solids (99mTc sulfur colloid-labeled chicken liver) and liquids (111In DTPA-labeled water). Naloxone, 5 mg intravenous bolus, accelerated the gastric emptying of both solid and liquid components, but this did not achieve statistical significance. These observations suggest that: morphine's inhibitory effect on gastric emptying and lower esophageal sphincter pressure may contribute to its potent emetic properties; the human lower esophageal sphincter and stomach may have opiate receptors and further investigations should be addressed to determining if endogenous opiates play a role in the modulation of sphincter pressure and gastric emptying in humans.