Paired helical filaments (PHF) are the main component of the Alzheimer neurofibrillary tangle; however, other elements, such as 10 and 15 nm straight filaments and granular amorphous components, are observed. In the present study, the localization of the antigenic determinants recognized by an antiserum to PHF fractions that does not recognize normal nervous tissue components is examined by electron microscopic immunocytochemistry. Employing the peroxidase-antiperoxidase procedure on neurofibrillary tangles in intact tissue, we found that the antiserum reacts with PHF and with granular amorphous material within the tangle. Following isolation of PHF by treatment with ionic detergent and labeling with immunogold, the antigenic determinants often occur at intervals rather than being uniformly distributed along the PHF. The distribution of the antigenic determinants recognized by this antiserum is similar to that previously observed for PHF determinants recognized by antibodies to neurofilament and microtubule-associated proteins. We conclude that PHF are heterogenous structures which contain PHF-specific as well as cytoskeleton-derived antigenic determinants.