The actions of .mu.-, and .delta.- and .kappa.-opiate receptor agonists were compared on the activity of single neurons in the brain stem, caudate nucleus and hippocampus of the rat, using the technique of microiontophores. In the brain stem and caudate nucleus the predominant effect of all the opiate agonists tested was depression of neuronal activity which was antagonized by naloxone. The selectivity of naloxone as an opiate receptor antagonist was indicated by its lack of effect on .gamma.-aminobutyric acid (GABA)-induced responses. In the hippocampus both .mu.- and .delta.-agonists mainly caused an increase in neuronal firing rates, though some neurons were depressed. In contrast, all the .kappa.-agonists, including the proposed endogenous ligand for the .kappa.-receptor, dynorphin, caused depression of neuronal activity. All of these effects were antagonized by naloxone. There was a clear distinction in the areas within the hippocampus in which the .mu.- and .delta.-agonists produced different effects. Neurons in the pyramidal cell layer were always excited by these drugs, whereas neurons in the granule cell layer of the dentate gyrus were always depressed by the same drug.