Neurofibrillary tangles are observed in several neurodegenerative disorders including Alzheimer's disease, progressive supranuclear palsy, and amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. The major components of neurofibrillary tangles are hyperphosphorylated tau proteins that can be directly detected in brain homogenates, using immunoblotting with specific immunological probes. To investigate whether tau proteins differ biochemically among various neurodegenerative disorders, we analyzed a series of brain samples from Guamanian patients in comparison with Alzheimer's disease, progressive supranuclear palsy, and normal aging. In Alzheimer's disease, these hyperphosphorylated tau proteins are composed of a triplet referred to as tau 55, 64, and 69, whereas in progressive supranuclear palsy, neurofibrillary degeneration is characterized by a tau doublet (tau 64 and 69). In the present study, characterization of tau proteins was performed by immunoblotting, on different cortical and subcortical regions of postmortem brain specimens from Guamanian natives. In all of the cases, biochemical data were always consistent with neuropathological findings. In contrast to Alzheimer's disease patients where the tau triplet is found mostly in cortical regions, a similar triplet was strongly detected in both cortical and subcortical areas in Guamanian patients. The tau profile differed quantitatively from case to case demonstrating that the Alzheimer's disease-related tau triplet had a heterogeneous regional distribution. These data suggest that the tau triplet found in amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam is similar to that observed in Alzheimer's disease, and the regional distribution of tau proteins differs in these disorders.