Clinical diagnosis of Alzheimer's disease (AD) is not fully satisfactory, and laboratory markers of this disease are not yet established. We report substantial regional Cerebral Blood Flow (rCBF) abnormalities in patients with documented early stages of the disease, when differential diagnosis is most critical. Thirty-six patients with carefully documented clinical diagnosis of early AD (mean disease duration, 3.25 +/- 1.80 years) and 12 elderly healthy controls participated in rCBF studies using the 133Xe inhalation method. Whole-brain perfusion was significantly (p less than 0.001) lower in the AD group, and a characteristic perfusion deficit was consistently found in temporoparietal cortex of the AD patients. Discriminant analyses demonstrated over 90% correct classification of the two groups. Two subgroups of patients with mildest disease manifestations were equally well discriminated. The similarity of these findings to those in late stages, which have been validated neuropathologically, offers indirect confirmation of validity and specificity. These results suggest that rCBF procedures may provide an accurate and sensitive laboratory marker for early AD.