BACKGROUND: This study aimed to evaluate regional cerebral blood flow (rCBF) changes using 99mTC-ECD SPECT (Ethylene Cysteine Diethylester Single Photon Emission Computed Tomography) and contemporary clinical responses such as cognitive and psychiatric symptoms and activities of daily living (ADL) after cholinesterase inhibitors (ChEI) treatment. METHODS: The subjects were eight probable Alzheimer's disease (AD) patients (four males and four females, mean age 69.63 years) who were recruited from the department of Neurology, at Yeungnam University Medical Center, between August 2000 and April 2002. The clinical diagnosis of AD was based on the DSM-IV and NINCDS-ADRDA criteria. Hachinski ischemic scores of all the patients were below 1. The mean treatment duration was 30.38 weeks which ranged from 24 to 44 weeks. Four patients received Rivastigmine (Exelon(r)) 12 mg after titration, and three patients received Donepezil (Aricept(r)) 10 mg during the whole period and only one patient had Donepezil 10 mg after the initial 5 mg for three weeks. The base line and follow up 99mTC-ECD SPECT studies were done on an average 6 days before the ChEI treatment and 4 days after finishing the study. RESULTS: The most significant increase in blood flow occurred in the bilateral parietal lobes (p<0.05). Reduction in the rCBF is more profound on the left hemisphere in the base line (p<0.05) and it achieved significant increase of rCBF after ChEI treatment compared with the right hemisphere (p<0.05). CONCLUSIONS: Treatment with ChEI for 30.38 weeks increased rCBF and overall increased in global cognitive functions including K-MMSE, ADAS-cog, CDR, CDR-SB, GDS, and NPI and ADCS-ADL scores.