A comparison was carried out of the effectiveness of intracerebroventricular or intraperitoneal administration of Leu-enkephalin to affect acquisition of a one-way active avoidance response, locomotor activity or shock sensitivity. Leu-enkephalin impaired acquisition of the avoidance response only when administered peripherally. In contrast, either central or peripheral administration of Leu-enkephalin increased locomotor activity in the open field, and Leu-enkephalin also produced analgesia when administered directly into the brain. The pattern of results suggests that Leu-enkephalin acts at a peripheral site to influence avoidance conditioning.