We tested the claim that inter-individual CBF variability in Alzheimer's disease (AD) is substantially reduced after correction for arterial carbon dioxide tension (PaCO(2)). Specifically, we tested whether the variability of CBF in brain of patients with AD differed significantly from brain of age-matched healthy control subjects (HC). To eliminate the CO(2)-induced variability, we developed a novel and generally applicable approach to the correction of CBF for changes of PaCO(2) and applied the method to positron emission tomographic (PET) measures of CBF in AD and HC groups of subjects. After correction for the differences of CO(2) tension, the patients with AD lost the inter-individual CBF variability that continued to characterize the HC subjects. The difference (¿K(1)) between the blood-brain clearances (K(1)) of water (the current measure of CBF) and oxygen (the current measure of oxygen clearance) was reduced globally in AD and particularly in the parietal, occipital, and temporal lobes. We then showed that oxygen gradients calculated for brain tissue were similar in AD and HC, indicating that the low residual variability of CBF in AD may be due to low functional demands for oxidative metabolism of brain tissue rather than impaired delivery of oxygen.