Penicillin-G has been used as a common agent to produce epileptic foci and interictal activity. The development of the interictal spikes has been associated with enhanced inhibitory effects. There is evidence that the opioid peptides play an important role in the production of some transient postictal behaviors. In order to test whether enkephalins are involved during the interictal activity, we analyzed immunoreactive met- and leu-enkephalin content and their release in vitro, after the injection of 50 IU of penicillin-G into the left amygdala. Male Wistar rats were injected once daily for 5 days, and sacrificed by decapitation (15 min after the penicillin-G infusion) on the fifth day. The rats were divided into two groups: 1. In one group we analyzed the tissue content of enkephalins in hypothalamus, hippocampus, amygdala, striatum and cerebral cortext. 2. The second group was used for the assessment of the in vitro release of enkephalins from amygdala slices. In the amygdala, the drug treatment produced an increase in the tissue content of IR-ME. No changes occurred in the other structures. The content of IR-Leu-enkephalin increased in all structures analyzed except the cerebral cortex. In vitro release of both enkephalins increased in drug treated animals. These results suggest that the enkephalins could be involved in postictal mechanisms, as a result of repetitive interictal spiking.