The effect of the metenkephalin analogue Hoe 825 on esophageal motility, fundic accommodation to distention, and migrating myoelectric complex was studied in 17 healthy volunteers. The metenkephalin analogue (40 micrograms i.v.) significantly increased the duration, amplitude, and propagation velocity of the postdeglutitive esophageal peristaltic contraction waves. It had no effect on the basal lower esophageal sphincter pressure but significantly decreased the completeness of the sphincteric relaxation from 85% +/- 5% on placebo to 70% +/- 7% (p less than 0.01). The metenkephalin analogue (40 micrograms i.v.) significantly decreased the fundic accommodation to distention. In doses ranging from 20 to 60 micrograms i.v. it induced a premature phase III of the migrating motor complex that started ectopically in the duodenum (without a gastric component) and migrated distally at a significantly higher velocity than a spontaneous phase III. It is hypothesized that the metenkephalin analogue induces these effects via an inhibition of the inhibitory nervous system.