Donepezil is a highly potent and selective reversible achetylcholinesterase inhibitor. [(11)C]Donepezil is prepared by methylation with [(11)C]CH(3)I of the corresponding 6'-O-desmethylprecursor. Tissue distribution in mice revealed a high uptake in brain and rapid clearance from the blood. Metabolization studies in mice indicated the formation of one (11)C-labeled polar metabolite that didn't penetrate the blood-brain barrier. Regional brain distribution in rabbits didn't reflect the measured achetylcholinesterase distribution in rabbit brain.