Abstract: Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal transduction. We have previously demonstrated that an antibody to an isozyme of PLC, PLC-δ, produced intense staining of neurofibrillary tangles in the brains of patients with Alzheimer's disease. In the present study, we investigated the protein level and activity of this enzyme in control and Alzheimer brains. Western blot analysis using a specific antibody for PLC-δ showed that the concentration of PLC-δ protein was significantly higher in the cytosolic fraction of Alzheimer's disease cortical tissue than in control brains. The activity of PLC-δ, which hydrolyzes phosphatidylinositol, was also investigated, and we found that PLC-δ activity was not significantly different in the Alzheimer and control cytosolic fractions. These results indicate that the specific activity of PLC-δ is decreased in Alzheimer brains and suggest that inactivation of PLC-δ might be related to the pathophysiology of this disease.