Capability of estrogen to alleviate spatial-learning deficits due to brain ischemia was evaluated in ovariectomized gerbils. Thirty-nine ovariectomized gerbils were physically trained to swim in a 90 cm-diameter round pool. The half of the ovariectomized animals received s.c. implantation of a Silastic capsule of estrogen, 1 week before ischemic assault. Transient brain ischemia was accomplished on experimental Day 1 by bilateral clipping of the common carotid artery for 15 min under pentobarbital and ketamine anesthesia. On Day 3 and onwards, daily Morris water-maze task was imposed. Although estrogen-treated non-ischemic animals spent longer time in the water, their swam distance were not different with the non-treated animals: estrogen had no effect on the spatial learning to take the shortest distance to get to the submerged table. In the ovariectomized non-treated gerbils, ischemia prolonged the time in the water and lengthened the swam distance. Among the ischemic gerbils, those given estrogen swam significantly shorter distance than the non-treated animals. The results indicate that estrogen alleviates the ischemia-induced deficits in the acquisition of the water-maze task. The results also defy previous association of estrogen with decreased acquisition of the water-maze task, which based principally on the prolonged time in the water.