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In order to investigate the effects of a partial cholinergic deafferentation on the functional activity of the cortex, the cerebral metabolic rate of glucose (CMRGlu) was measured with positron emission tomography and 18F-2-fluoro-2-deoxy-D-glucose in 5 baboons (Papio anubis) both before and serially following stereotaxic electrocoagulation of the left nucleus basalis of Meynert (NbM). Four days postlesion, significant metabolic depression was present in the entire ipsilateral cerebral cortex, most marked in the frontotemporal region, and which slowly recovered close to normal within 6-13 weeks. Postmortem studies showed that the lesions were located largely in the NbM, and that a significant decrease in choline-acetyltransferase (ChAT) activity was present in the ipsilateral frontal, temporal and parietal cortices. The animal with the most limited histological lesion showed the least decrease in both ChAT activity and CMRGlu. There was a highly significant linear correlation between the regional cortical decreases in CMRGlu (early postlesion data) and in ChAT activity. These results indicate that cholinergic deafferentation induces a proportional metabolic depression in the cortex. However, compensatory mechanisms operate to restore the cortical metabolic activity gradually despite sustained cholinergic denervation, pointing to pre- and/or postsynaptic adaptation (plasticity). Moreover, unilateral NbM lesions also induced a significant reduction in contralateral CMRGlu, which also demonstrated recovery. Several mechanisms are discussed to explain this contralateral effect, but the most likely implicates a transcallosal depression of function as a result of ipsilateral effects of the NbM lesion. These metabolic effects of cholinergic deafferentation in the primate provide new insight into the mechanisms of cortical dysfunction, and the recovery thereof, following subcortical lesions. In addition, our findings have some relevance to the cortical consequences of cholinergic deafferentation observed in dementia of Alzheimer type.