Antibodies to neurofilaments and the microtubule-associated protein, tau, have been used with anti-paired helical filament (PHF) serum to study Alzheimer neurofibrillary tangles. Tangles and their constituent PHF contain epitopes derived from or cross-reactive with both neurofilaments and tau proteins. These same structures are labelled with anti-PHF antibodies. A component of the anti-PHF serum is against tau proteins. We conclude that PHF are at least in part derived from an abnormal neuronal cytoskeleton.