There have been many advancements in the pharmacologic treatment of schizophrenia; however, negative symptoms and cognitive impairment remain an intractable part of this illness. Donepezil is an anticholinesterase inhibitor with cognitive enhancing effects approved for the treatment of Alzheimer disease that has shown some benefit in the treatment of schizophrenia. In this study, 15 inpatients at a state hospital with a history of schizophrenia were administered donepezil in a randomized, double-blind crossover design. Neurocognitive testing and psychiatric ratings were completed at baseline and at regular intervals for 18 weeks. Results indicated that donepezil treatment was associated with modest improvements in psychiatric symptoms and improved verbal learning. These results suggest that donepezil may be helpful as adjunctive therapy for the treatment of psychiatric symptoms and cognitive impairment in a subgroup of schizophrenic patients.