We report on seven patients with Alzheimer’s disease who experienced behavioral worsening following the initiation of donepezil. All were diagnosed with Alzheimer’s disease according to DSM-IV criteria. Their mean age was 76.4 years, and their mean score on the Mini-Mental State examination R5115511CHDBABFC was 18.4. Five patients had experienced dementia-related delusions and irritability before donepezil use; one had a history of major depression; and the other, a history of somatization disorder. At the time of donepezil initiation, four were being treated with sertraline, one with paroxetine, one with venlafaxine, and four with risperidone. All began a regimen of donepezil, 5mg/day. After 4–6 weeks, the dose of five patients was increased to 10 mg/day of donepezil. In the other two cases, donepezil was discontinued after 5 weeks, in one case because of gastrointestinal symptoms and in the other because of increasing agitation. After an average of 7.3 weeks (range: 1–13 weeks) following initiation of donepezil, all seven patients experienced a recurrence of previous behavioral problems. Five became more agitated, one became depressed, and the patient with somatization disorder became more anxious and somatically preoccupied. An additional case (not evaluated by us) came to our attention: a demented nursing home patient, after starting donepezil, resumed playing the piano but also resumed trying to leave the nursing home, a behavior that had resolved as her dementia progressed.