In this study we tested the hypothesis that synapse loss contributes to decreased regional cerebral blood flow (rCBF) in Alzheimer disease (AD). We compared antemortem rCBF and postmortem analysis of synaptophysin, as a measure of synapse loss, in 13 cases of AD. rCBF studies were performed using inhaled xenon gas (Xe-133), which yields quantitative results. Synapse loss was evaluated in postmortem brain samples using an enzyme-linked immunosorbant assay (ELISA) that measures synaptophysin, with results expressed as picomoles synaptophysin/10 mg brain. Synaptophysin was expressed either as concentration (QS method) or as the ratio of the concentration to the combined results in frontal, temporal and parietal lobe (RS method). There was no correlation between synapse loss and rCBF using the QS method and only borderline significance between right SPECT and right temporal synaptophysin using the RS method. The results of this study suggest that synapse loss may be a minor contributor to the decreased rCBF observed in AD.