The possible importance of opioid peptides in the induction of long-term potentiation (LTP) was investigated in the perforant path-granule cell system. A high-frequency train (400 Hz) was delivered to the lateral or medial perforant path, during push-pull perfusion of the dentate molecular layer with artificial cerebrospinal fluid (CSF) alone, or with CSF containing naloxone (10(-4) M). Naloxone effectively blocked the induction, but not the maintenance of LTP in the lateral perforant path, a putative proenkephalin system. Naloxone did not affect the production of LTP in the medial pathway. These findings suggest that activation of naloxone-sensitive receptors is necessary for the full expression of LTP in the lateral perforant pathway.