Observations were made with the electron microscope on biopsies from the frontal cerebral cortex of four patients showing the clinical symptoms of advanced Alzheimer's disease (AD). Sections from all four biopsies showed neuronal dendrites, and to a lesser extent, perikarya, packed with paired helical filaments (PHFs) and a correlated complete loss of the normal content of microtubules. It was usually impossible to visualize the beginning and end of the PHF since it passed out of the plane of section. However, not infrequently, PHFs could be seen apparently arising at or from the surfaces of cytomembranes. Such membranes (in perikarya or dendrite) often formed irregular stacks or lamellated bodies. These membranes were invariably agranular (i.e. not studded with ribosomes) and so might be considered as pathological forms of smooth endoplasmic reticulum (SER). A correlation is established between the known biochemical nature of PHFs and their postulated membrane origin.