The activity of the pyruvate dehydrogenase complex (PDHC; EC, EC 2.3.12, and EC was reduced to about 30% of control values in histologically unaffected occipital cortex of the brains of patients with Alzheimer's disease, as well as in histologically affected frontal cortex. In contrast, activity of another mitochondrial enzyme, glutamate dehydrogenase, was normal. Neither age nor time untill postmortem study correlated significanctly with PDHC activity in either Alzheimer or control samples, and PDHC was not inactivated significantly on incubation with homogenates of either Alzheimer or control brain. Antibodies against the highly purified bovine PDHC inhibited Alzheimer and control PDHC equally per unit of enzyme activity. Immunoblots also indecated that the PDHC antigens were not different in normal and Alzheimer brain. This antibody, however, inhabited Alzheimer PDHC more effectively than it did control PDHC, based on milligrams of protien, suggesting a reduced amount of normal PDHC protien. Other data suggest that the PDHC deficiency is related to mitochondrial damege and to impaired calcium homeoestasis in Alzheimer nerve cells, which may then mediate a variety of other cellular impairments.