The relationship between the entorhinal cortex and learning behavior was examined. The initial stage of Alzheimer's disease has been shown to be characterized by neuropathological alteration in the entorhinal cortex, with the appearance of the greatest number of neuronal tangles and severe neuronal loss in comparison with other brain regions involved. This entorhinal cortex, because of its anatomical relationship to the hippocampus, may play a crucial role in memory formation. In this study, rats with bilateral ibotenic acid-induced lesions of the entorhinal cortices were tested for acquisition of passive and active avoidance learning tasks. These animals displayed no sensorimotor disturbances as shown by evaluation of locomotor activity and shock sensitivity. However, they did show impair acquisition of passive and active avoidance responses. On the other hand, when the lesions were induced after training, there was no extinction of the acquired passive and active avoidance responses. The results demonstrate the importance of the entorhinal cortex in learning acquisition and indicate that rats with partial neuronal loss in the entorhinal cortex may be a useful model for studying the memory disturbance of Alzheimer's disease.