In slices of guinea pig brain, intracellular recordings were obtained from neurones of the ventromedial nucleus of the hypothalamus (VMH). [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO), an agonist selective for mu-opioid receptors, caused an inhibition of spontaneous firing activity and a membrane hyperpolarization. This effect was reversible, concentration-dependent and could be blocked by naloxone. DAGO directly inhibited VMH neurones since its effect persisted when the slice was perifused with a solution that blocks synaptic transmission. The hyperpolarization induced by DAGO was associated with a marked decrease in membrane input resistance and it was reversed in polarity at membrane potentials 30-40 mV more negative than the resting potential. A chloride current did not contribute to the hyperpolarization brought about by DAGO. We conclude that DAGO inhibits VMH neurones, probably by opening membrane potassium channels.