A study was made of the effects of opioid peptides on the spontaneous firing of oxytocin-responsive non-pyramidal neurones in hippocampal slices. D-Ala2-Gly-ol5-enkephalin (DAGO), a mu-opiate agonist, decreased or even suppressed the firing of these neurones, an effect reversed by naloxone. In contrast, U-50,488, a kappa-opiate agonist, had no effect. When the slices were synaptically uncoupled by elevating the concentration of external magnesium, oxytocin still excited non-pyramidal neurones and DAGO still inhibited them. Thus, opiates and oxytocin exerted direct, opposite effects on the same population of neurones, which apparently bear mu-type receptors. An indirect action of opioids on the excitability of pyramidal cells was apparent and is probably mediated by the same interneurones, since the amplitude of the depolarizing component of the synaptic potential elicited by stimulation of Schaffer's collaterals was increased in the presence of DAGO.