Pedunculopontine nucleus areas were lesioned bilaterally in the rat by local injection of kainic acid. When rats so treated were tested for active avoidance behavior in shuttle boxes we found that their avoidance acquisition was completely abolished, whereas their intertrial locomotor activity and escape behavior were not affected. In the lesioned rats, choline acetyltransferase activity in the medial thalamus and substantia nigra decreased, but not in the lateral thalamus, hippocampus, or cerebral cortex. These findings suggest that the cholinergic pedunculopontine-medial thalamus projection plays an important role in memory acquisition in the rat.