OBJECTIVE The objective of this study was to evaluate donepezil, an acetylcholinesterase inhibitor, in the treatment of frontotemporal dementia (FTD). METHODS Twelve patients with FTD who received donepezil for six months were compared with 12 FTD controls on behavioral measures. RESULTS The groups did not differ on most variables at baseline or at six months; however, the donepezil group had greater worsening on the FTD Inventory. Four treated patients had increased disinhibited or compulsive acts, which abated with discontinuation of the medication. CONCLUSION There were no changes in global cognitive performance or dementia severity; however, a subgroup of patients with FTD can experience worsening of symptoms with donepezil.