A memory deficit model has been developed following bilateral internal capsule lesions in rats. During 12-49 days after internal capsule lesions, the rats showed a marked impairment of active avoidance acquisition in a step-through apparatus, while they exhibited no observable change in native behaviors, except a slight increase in exploratory activity. A passive avoidance task in the same apparatus was also impaired in internal capsule lesioned rats when examined after one-trial training, though the task was gradually acquired by repeated trainings. Moreover, the retention of both the active and passive avoidance responses in well-trained rats deteriorated after internal capsule lesions. On the other hand, internal capsule-lesioned rats did not perform any worse than sham-operated rats in a T-maze spontaneous alternation behavior and in a habituation response to a novel environment. In the frontal cortex and striatum of internal capsule-lesioned rats, there was a significant decrease of dopamine, serotonin and their metabolites, but no change of acetylcholine levels. The acquisition deficit of active avoidance in internal capsule-lesioned rats was improved by thyrotropin-releasing hormone (TRH, 10 mg/kg, i.p.) and L-6-ketopiperidine-2-carbonyl-L-leucyl-L-proline amide (RGH-2202, 10 mg/kg, i.p., 0.2 and 1 mg/kg i.v.), but not by physostigmine sulfate (0.2 mg/kg, i.p.). These results indicate that bilateral internal capsule lesions in rats induce long-term memory deficits which are paralleled with a decrease of the contents of monoamines and their metabolites and improved by TRH and RGH-2202.