Paired helical filaments (PHFs) are one of the hallmark pathologies of Alzheimer's disease (AD). PHFs occur in three intracellular locations, although hitherto, it was not known whether all PHFs are structurally homogeneous. Parietal cortex biopsies were taken from five patients with a clinical and histopathological diagnosis of AD and processed for electron microscopy. Photomicrographs were then taken of PHFs in neurofibrillary tangles (NFTs), neuropil threads (NTs) and neuritic plaque (NP) neurites and their dimensions measured. The mean half period, maximum and minimum widths of PHFs in NFTs were significantly smaller than those in NTs or NP neurites. The mean half period and maximum width of PHFs in NTs were similar to those in NP neurites. These results reveal the presence of two distinct PHF populations and investigation of their relationship may shed light on the pathogenesis of AD. (C) 1997 Elsevier Science Ireland Ltd.