Donepezil is a highly potent and selective reversible achetylcholinesterase inhibitor. [11C]Donepezil is prepared by methylation with [11C]CH3I 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 11C-labeled polar metabolite that didnt penetrate the blood-brain barrier. Regional brain distribution in rabbits didnt reflect the measured achetylcholinesterase distribution in rabbit brain.