Methionine-enkephalin, leucine-enkephalin and beta-endorphin were applied in known concentrations to an in vitro preparation of myenteric neurons from the guinea-pig ileum. All 3 substances caused a rapid, reversible and dose related inhibition of the firing of myenteric neurons induced and recorded with extracellular suction electrodes. This inhibition of firing occurred at low agonist concentrations (1-300 nM) and was reversed by naloxone and a benzomorphan narcotic antagonist. The inhibition persisted in solutions which were completely free of calcium ions -- thus indicating that the observed effect is taking place directly on the neuron from which the recording is made, and that calcium ions are not required for this inhibitory action of endorphins on neuronal firing.