A pilot study was conducted to examine if donepezil could enhance cognitive function in patients with schizophrenia. Fifteen subjects who were on stable olanzapine treatment were entered into a 6-week open-labeled trial of donepezil. Subjects received baseline and end-of-study P50 and neuropsychological assessments. Donepezil treatment resulted in significant improvement in manual dexterity. There were moderate improvements in verbal recall memory and visual memory and processing speed, with smaller changes in P50 and verbal recognition memory. There was no effect on an attention measure. There were no changes in either positive or negative symptoms. These results suggest that cholinergic tone modulation may enhance selective behavioral functions in patients with schizophrenia, but further study is required to delineate the full extent of the potential benefit of this approach.