Previous comparisons between presenile Alzheimer's disease (AD) and senile dementia of the Alzheimer type (SDAT) did not control for disease severity and duration. In the current study, 18 patients with each diagnosis were matched for disease duration, cognitive dysfunction, and behavioral symptoms (using the modified Mini-Mental Status [mMMS] examination and the Blessed Dementia Rating Scale [BDRS] ). Regional cerebral blood flow (rCBF) was quantified by the 133xenon inhalation technique, and several indices of tissue perfusion were examined. The two variables of primary interest were relative gray-matter relative weight (35% in presenile patients versus 39% in senile patients and healthy control subjects, p = 0.006), with neither perfusion nor disease severity differences between the two dementia samples. This loss of gray matter was significantly related to both severity and duration of disease in the patients with presenile AD, but not in patients with SDAT. These findings lend support ot previous suggestions of greater degenerative process in presenile AD and confirm the need to examine and control age of onset in future investigations of AD. Further, correlation analysis suggests greater proportion of common variance among clinical and physiological indices in presenile AD.