Neurofibrillary tangles occur in a number of apparently distinct neurodegenerative diseases and in normal aging of the human brain. Antibodies raised against Alzheimer's disease paired helical filaments immunolabel the tangles seen in all other tangle-associated disorders examined to date. The neuronal microtubule-associated protein, tau, has recently been identified as an antigenic component of neurofibrillary tangles and senile plaque neurites in Alzheimer's disease. Three different polyclonal antibodies with strong tau immunoreactivity are examined in this study. These antibodies were found to immunostain tangles in normal aged brain and in brains affected by a range of neurodegenerative disorders, including Down's syndrome, Alzheimer's disease plus Parkinson's disease, progressive supranuclear palsy, and the parkinsonism-dementia complex of Guam, as well as Pick bodies in Pick's disease. The findings further illustrate the relative nonspecificity of neurofibrillary lesions in neurodegenerative disorders.