In intact tissue, [D-Ala2,MePhe4,Gly-ol5]enkephalin (10(-5) M; mu-ligand), diminished short-circuit current (Isc) and increased water, Na+ and Cl- net fluxes in vitro under open circuit conditions; it also inhibited L-valine absorption and L-valine-dependent variations of short-circuit current (delta Isc,val). Naloxone (10(-6) M) antagonized these effects. In the absence of the muscularis and myenteric plexus this enkephalin or morphine (mu-ligand) reduced Isc and delta Isc,val. These enkephalin effects occurred at different times. Different concentrations of enkephalin were tested for their effects on delta Isc,val. [D-Ala2,D-Leu5]enkephalin (mainly a delta-ligand) significantly decreased Isc but not delta Isc,val. The reduction of L-valine absorption does not depend on the effects on basal ion transport. Interaction of opioids with mu-receptors located in the submucosal plexus and/or in the epithelial cell accounts for this reduction. This enkephalin effect seems to be at least partially under the control of the myenteric plexus.