A simple and reliable method for the preparation of an ischemia-induced amnesic model was developed in mice and the model animals were employed for screening of the anti-amnesic effect of drugs. Under light thiopental anesthesia the bilateral carotid arteries were exfoliated from the surrounding tissues. Each artery was threaded through a small polyethylene tube, and the incision was sutured, leaving the tip of the tube and both ends of the thread out of the skin. To prevent the tube from falling off, both ends of the thread was ligated at the tip of the tube. Cerebral ischemia was attained by pulling the artery into the tube, and the occlusion was rapidly released by cutting the ligation in the thread and taking off the tube. Twenty-four hours after the surgery, the animals were used for the one trial passive avoidance learning test. In ddY strain mice, the amnesic state was obtained by 5 to 30 min cerebral ischemia, which was applied immediately after the acquisition trial. Mice of the ICR strain were more sensitive to the ischemic treatment and 2 min occlusion of the carotid arteries resulted in a high degree of amnesia. A potent prolyl endopeptidase inhibitor, Z-thiopro-thiazolidine, and 2 novel pyrrolidone derivatives, p-chlorobenzyl-2-pyrrolidone-5-carboxylate and N-(2-pyridylmethyl)-2-pyrrolidone-5-carboxamide, improved the acquisition of the passive avoidance response in the ischemia-induced amnesic models.