1 The actions of morphine, methionine and leucine enkephalin, administered electrophoretically, were studied on supraspinal neurones in the cortex and brainstem of the rat anaesthetized with urethane and on spinal Renshaw cells and dorsal horn interneurones in the cat anaesthetized with pentobarbitone.2 The majority of Renshaw cells and cortical and brainstem neurones were excited by all three compounds although some supraspinal neurones were depressed.3 Naloxone reversibly antagonized both excitatory and depressant actions of morphine and enkephalin. Acetylcholine-induced excitation but not amino acid-induced excitation was also antagonized by naloxone.4 Neither morphine nor the enkephalins had any naloxone-reversible action on dorsal horn neurones when ejected from conventional multibarrelled electrodes. However, morphine but not enkephalin, administered into the substantia gelatinosa region of the spinal cord selectively reduced responses to noxious stimuli of neurones in deeper laminae. Naloxone administered into the same region antagonized this action of morphine.5 Intravenous morphine also antagonized responses of dorsal horn neurones to noxious stimuli and subsequent intravenous naloxone reversed this effect.6 It was concluded that the excitatory and inhibitory effects of morphine and enkephalin on central neurones may be mediated by actions on different opiate receptors and that depression of noxious responses of dorsal horn neurones may be relevant to the analgesic action of morphine.