We evaluated both hippocampal blood flow and hippocampal gray matter volume using single photon emission tomography and magnetic resonance imaging in the same individuals with Alzheimer's disease (AD) and in age-matched controls. The hippocampal blood flow was not significantly lower in mild AD patients (n = 21, Mini-Mental State Examination (MMSE) 23.3+/-2.1) than in controls (n = 16) with a 57% overlap. The hippocampal blood flow was significantly lower in advanced AD patients (n = 22, MMSE 15.4+/-3.2) than in controls. The hippocampal gray matter volume was significantly smaller in mild AD patients than in controls, although a 43% overlap was present. There was no significant difference in the hippocampal gray matter volume between the mild and advanced AD patients. The combination of measurements of hippocampal blood flow and gray matter volume discriminated 71% of mild AD patients from controls. These results suggest the usefulness of a combined analysis of hippocampal blood flow and gray matter volume for the early diagnosis of AD.