To evaluate the pathophysiology of frontal lobe dementia (FLD), the authors compared regional cerebral blood flow (rCBF) in matched groups of FLD, probable Alzheimer's disease (AD), and major depression patients and normal control subjects (n = 7 each). The planar xenon-133 technique allowed full quantification of cortical perfusion and estimates of the relative weight of gray matter (wg). FLD patients showed lower blood flow and wg in the frontal cortex than the other groups. Mean cortical perfusion was correlated with cortical wg in the FLD group only. These findings 1) suggest that matched reductions of frontal gray matter weight and perfusion occur in FLD and 2) support the use of rCBF in distinguishing FLD from AD and severe depression.