The effects of intraperitoneal (IP) administration of the endogenous opioid peptide, [Leu]enkephalin (LE), on avoidance conditioning in rodents were investigated. At a dose of 30 micrograms/kg (IP), LE enhanced acquisition of a one-way step-through active avoidance response when administered 2 minutes before training to Swiss Webster mice. [Leu]enkephalin produced a U-shaped dose-response function because both lower and higher doses of LE did not affect avoidance responding. [Leu]enkephalin-induced enhancement of avoidance acquisition was also observed in Sprague-Dawley rats; the intraperitoneal injection of 10 micrograms/kg LE, administered 5 minutes before training, enhanced acquisition of a jump-up one-way active avoidance response. When administered to Sprague-Dawley rats immediately after training, LE (30 micrograms/kg IP) enhanced jump-up avoidance responding at test 24 hours after peptide injection. Previously, we found LE to impair acquisition in the same tasks in both rats and mice, also at microgram doses, and also in a U-shaped manner. Thus, LE can either enhance or impair learning within the same species and the same task; these findings are in agreement with recent theoretical proposals regarding the nature of compounds, such as LE, that modulate learning and memory.