We found that rats with unilateral AF64A lesions of the nucleus basalis of Meynert (nbM) showed significant impairment of active avoidance and Morris water maze learning. Impairment of active avoidance learning almost subsided within one month but impairment of Morris water maze learning persisted 5 months later. Two weeks after production of the lesion, choline acetyltransferase (ChAT) activity was reduced by 45% in the frontal cortex (FC), but not in the hippocampus or corpus striatum. The decreased ChAT activity in the FC gradually recovered, but it was still reduced by 20% even after 20 weeks. In contrast, ChAT activity on the contralateral side of the FC began to increase from 5 weeks onwards. Histological examination also indicated that loss of cholinergic fibers in the FC gradually recovered with time after induction of the lesion. The results from the present study suggest that specific learning (Morris water maze) tasks involve the cholinergic system and that recovery of cholinergic function (ChAT) may be related to plasticity of the contralateral FC.