Cytochrome c oxidase (COX) is deficient in both peripheral tissue and brain of Alzheimer's disease (AD) patients and may be of pathogenic significance in AD. We purified COX from AD brains (n = 3) and control brains (n = 3) and characterized the enzyme kinetically and spectrally. Purified AD brain COX displayed anomalous kinetic behavior compared with control brain COX in that the low Km binding site was kinetically unidentifiable. For purposes of comparison, we purified COX from a standard beef heart preparation and found normal kinetic behavior. AD brain COX may be structurally abnormal and may make an important contribution to the bioenergetic defect seen in AD.