Dystrophic neurites (DNs) are one of the neuropathological characteristics of Alzheimer's disease (AD). Previously, it has been suggested that tau-immunoreactive DNs are of dendritic origin and that axonal and dendritic dystrophic neurites are morphologically indistinguishable. In the present study, two monoclonal antibodies, tau-1 and PHF-1, were used to examine sections of the hippocampal formation from AD and normal aged brains. Both antibodies stained dendritic DNs as well as axonal DNs. Axonal DNs were clearly seen in axonal fiber tracts, white matter and hippocampal terminal regions. Axonal DNs arising from neurofibrillary tangles were easily detected in CA3 and CA1. The morphological appearance of axonal DNs varied with the neuron type from which it originated. The most distinctive feature of tau-1 or PHF-1 immunostained axonal DNs was their uneven contour, alternating swollen and shrunken segments and short rod or cone shaped fragments. In contrast, dendritic dystrophic neurites are thicker and more tortuous. It appears that while DNs are both dendritic and axonal in origin, axonal DNs are more prevalent and widespread in the AD brain than previously realized and may represent one of the main pathological lesions in AD.