Alz-50 is a monoclonal antibody that stains the neurofibrillary pathology of Alzheimer's disease, as well as apparently normal nerve cells that are at risk of developing neurofibrillary tangles. On immunoblots it recognizes microtubule-associated protein tau and proteins of 60-68 kDa that are associated with Alzheimer's disease. We have used recombinant tau proteins expressed in E. coli to map the Alz-50 epitope to amino-terminal residues 2-10, a region common to all known human tau isoforms. A direct correspondence between immunoblots and histological staining was established by the abolition of Alz-50 staining following adsorption with recombinant tau proteins retaining amino-terminal sequences. This suggests that tau pathology represents an early event in the development of the neurofibrillary pathology of Alzheimer's disease.