ENDOGENOUS ligands for the opiate receptor have recently been described. The first to be characterised were methionine-enkephalin and leucine-enkephalin, penta-peptides isolated from porcine brain by Hughes et al. and subsequently synthesised1. The enkephalins are also found in high concentrations in the myenteric plexus of the guinea-pig ileum2,3, a neuronal network which is widely used as a model in investigations of narcotic action4. In the myenteric plexus, narcotic analgesics inhibit the neuronal firing which can be recorded with a glass suction electrode5,6. This action is stereospecific, is reversed by narcotic antagonists such as naloxone and is not dependent upon the presence of any synaptic input to the neurones6. The endogenous presence of enkaphalin in brain prompted an examination of its effects when applied by iontophoresis to units whose activity was recorded extracellularly7–10. We have adopted an alternative approach in which known concentrations of enkephalin are applied to isolated ganglia of the myenteric plexus whilst recording neuronal activity. The results indicate that low concentrations of the enkephalins act on the myenteric neurones to inhibit their firing.