Butyrylcholinesterase histochemical techniques were applied to vibratome sections of several cortical areas from the brains of non-demented aged and of Alzheimer's disease patients. At the light microscope level, all the senile plaque types and all the structures with neurofibrillary degeneration showed butyrylcholinesterase reaction product, whereas nearby neuronal perikarya and axons on the same slides remained unstained. Areas containing stained elements were selected, re-sectioned, and finally observed under the electron microscope. Focusing on the sites of neurofibrillary degeneration, butyrylcholinesterase reaction product was found in both intra- and extracellular neurofibrillary tangles, in neurites associated with plaques, and in neuropil threads that were either axons or dendrites. This reaction product was exclusively located over filament bundles, and sometimes covered them so completely that they could not be identified. When the filaments were only partially covered, it was possible to identify them as either paired helical filaments or straight filaments. Occasionally, neurofibrillary tangles, neuropil threads and plaque-associated neurites, all of them containing either paired helical filaments or straight filaments, were found to be completely free of butyrylcholinesterase reaction product. The origin and possible role of butyrylcholinesterase, which is ultrastructurally localized over elements presenting neurofibrillary degeneration, is discussed.