Intraneuronal fibrillary tangles are prominent features of several neurological diseases, including especially Alzheimer presenile and senile dementia, and to a much lesser degree in the normal aged human brain. These tangles are made up of abnormal fibrillar elements each about 22 nm at its widest, periodically reduced to 10 nm at about every 80 nm. Each abnormal fiber seems to be a pair of 10 nm filaments helically wound around each other. In this study the protein subunit of these paired helical filaments isolated from cases of Alzheimer's dementia was compared with the major protein subunits of normal neurofilaments and neurotubules by two-dimensional peptide maps of the tryptic or chymotryptic digests of these proteins labelled with 125I. The paired helical filament protein is very similar in its peptide maps to identically treated major neurofilament protein and to the beta monomer of neurotubule, while it is not so similar to the alpha tubulin. These data suggest that the paired helical filament protein subunit is closely related chemically to the normal neurofilament protein subunit, and the beta tubulin.