The effect of perforant path kindling on the levels of mRNAs coding for proenkephalin and prodynorphin in hippocampus and frontal cortex of rats was measured using RNA blot analysis. In rats showing stage 3 kindled seizures, after consecutive stimulation of the right perforant path, a decrease in the level of prodynorphin mRNA and an increase in levels of proenkephalin mRNA in the ipsilateral hippocampus was found. In addition, the levels of prodynorphin were also decreased in the contralateral hippocampus. No changes in the opioid peptide mRNAs were found in the frontal cortex of the animals. The altered mRNA levels in the hippocampus returned to normal 8 days following cessation of the electrical stimulation. However, at that time a single stimulus was still effective in producing stage 3 kindling seizures. These findings indicate that (1) the opioid peptide gene expression in the hippocampus can be transynaptically altered by kindling of the perforant path and (2) that the opioid peptides may play a role in the development, but not in the maintenance of kindling.