Cholinesterase inhibitors improve or stabilize cognitive impairment in patients with Alzheimer's disease (AD). The purpose of this study was to detect brain perfusion changes and the effects of rivastigmine, an acetylcholinesterase inhibitor on single photon emission computed tomography (SPECT) before and after treatment. Fifteen patients who fulfilled the clinical criteria for probable AD of mild to moderate severity, as put forth by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association, and as specified by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were included in the study. A control group of 15 healthy individuals from the same age and education range was included in the study. Before treatment was begun, Mini Mental State Examination (MMSE) tests were performed on all patients to evaluate cognitive function. All patients underwent baseline SPECT for evaluation of 25 different brain regions. Rivastigmine 3 mg/d was given for the first 4 wk of treatment; the dosage was then increased to 6 mg/d. The MMSE and SPECT were repeated 6 mo after the start of treatment. SPECT findings revealed that rivastigmine did not significantly affect brain perfusion in AD cases except in the inferior frontal lobe, despite stabilization and improvement noted in MMSE scores during treatment. Rivastigmine treatment of patients with AD did not significantly change brain perfusion as seen on SPECT, except in the inferior frontal lobe, but cognitive performance was stabilized or improved during the treatment course. These findings suggest the need for additional, larger studies to investigate the effects of acetylcholinesterase inhibitors on regional cerebral blood flow.