The brain peptides alpha- and beta-endorphin, leucine- and methionine-enkephalin, as well as the opiate normorphine, have been evaluated by microiontophoresis for their effects on neuronal activity in several regions of the rat brain. In cerebral cortex, brainstem, caudate nucleus, and thalamus, most responsive cells were inhibited by the peptides and by normorphine, while in hippocampus all responsive cells were excited. Both inhibitory and excitatory responses were blocked by the narcotic antagonist naloxone. Occurrence of responsive cells encountered in a particular region was loosely correlated with density of stereospecific opiate binding sites as reported by others. These results are consistent with the hypothesis that the endorphins and enkephalins may represent a new class of central neurotransmitters; among other functions, these peptides may play a role in the regulation of behavior and the expression of psychopharmacological agents such as the opiate alkaloids.