When given before or after training, Leu-enkephalin impairs later retention of learning. To replicate these findings, Experiment 1 determined if Leu-enkephalin impairs retention when administered after inhibitory avoidance training. Posttraining injection of 100.0 micrograms/kg of Leu-enkephalin impaired retention relative to saline controls or those receiving a lower dose of this peptide. Since Leu-enkephalin does not cross freely from the blood stream into the brain, this peptide may exert its influence on mnemonic processes by activating peripheral receptors that transmit neural messages to the brain via the vagus nerve. In Experiment 2, 100.0 micrograms/kg Leu-enkephalin impaired retention in unoperated and sham-operated animals although vagotomized animals did not differ significantly from these groups or saline controls. These results suggest that subdiaphragmatic vagotomy may not be sufficient to disrupt the mnemonic effects of Leu-enkephalin. Alternatively, the vagus nerve may be one pathway but not the only pathway by which the activation of peripheral systems may influence the memory storage process.