Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal transduction. We demonstrated that an antibody to an isozyme of PLC, PLC-delta 1, produced intense staining of neurofibrillary tangles (NFT) in the brains of patients with Alzheimer's disease (AD). Western blot analysis using a specific antibody for PLC-delta 1 showed that the concentration of PLC-delta 1 protein was significantly higher in the cytosolic fraction of AD cortical tissues than in controls. The activity of PLC-delta 1, which hydrolyzes phosphatidylinositol, was not significantly different in the Alzheimer and control cytosolic fraction, indicating that the specific activity of PLC-delta 1 is decreased in Alzheimer brains. Western blot analysis also showed that the concentration of PLC-delta 1 and PLC-gamma 1 was significantly lower in the membraneous fraction of AD cortical tissues than in controls. These results suggest a differential involvement of PLC isozymes in AD.