The immunoreactivity of neurofibrillary tangles (bundles of abnormal filaments) in Alzheimer's disease was compared in photonic and electron microscopy using antisera against the microtubule- associated protein tau, against isolated tangles, against ubiquitin and using monoclonal antibodies against neurofilament proteins. Only a sub-population of tangles is labeled in situ by the anti-ubiquitin serum and some tangles are unlabeled by any of the antibodies used. Double immunolabeling in electron microscopy shows, however, that ubiquitin epitopes can coexist with tau and neurofilament epitopes on a same abnormal filament. These results indicate that in situ ubiquitin immunoreactivity (and to a lesser extent tau and neurofilament immunoreactivity) is not an obligatory feature of these abnormal filaments and suggest that their antigenic composition could evolve in affected neurons.