The electrophysiological effects of a highly selective mu opioid agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO) were investigated on S and AH myenteric neurons in the guinea-pig ileum. Administration of DAGO (500 nM) caused a mean membrane hyperpolarization (+/- S.E.M.) of 7.8 +/- 0.5 mV in 58 of 138 S neurons, associated with a decrease in input resistance from 158 +/- 18 to 132 +/- 13 m omega. DAGO also produced a significant decrease in the mean amplitude of the cholinergic fast excitatory postsynaptic potentials (EPSPs), from 12.0 +/- 1.1 to 6.6 +/- 1.4 mV in 13 of 27 S neurons. On the other hand, in AH neurons, DAGO did not significantly affect the membrane potential, input resistance, action potential configuration, slow after-hyperpolarization or the antidromic action potential. The experiments indicate that the acute effects of mu opioids in the guinea-pig ileum are confined to a subpopulation of a single electrophysiological class of myenteric neurons.