The demonstration in the midgut of the insect Leucophaea of specific high affinity binding sites for a synthetic opioid represents the first report on neuropeptide binding in the digestive system of an invertebrate. Binding of the enkephalin analog DAMA ( d-Ala 2, Met 5-enkephalinamide) is monophasic, saturable with respect to the concentration of the radioligand used, and stereospecific. Binding of the opiate antagonist naloxone to midgut homogenates is also monnophasic, saturable, and stereospecific. The binding site density for DAMA is reduced by sodium and increased by manganese. By contrast, binding of naloxone is enhanced by sodium and unaffected by manganese. Lithium is equipotent with sodium in altering these values. Prolonged exposure of the organ to naloxone increases its binding capacity for DAMA. In midguts deprived of their autonomic innervation by severance of the recurrent nerve the binding capacity for the synthetic opioid is lower than in controls. Also, such ‘denervated’ organs are no longer affected by prolonged naloxone treatment. Results of tests for the presence in the midgut of non-peptidergic neurotransmitters (dopamine, norepinephrine) possibly operating in response to enkephalinergic signals, have thus far been negative. The results strongly suggest the existence in the digestive tract of this invertebrate of opioid receptors comparable to those in analogous mammalian systems.