A rabbit antiserum was raised against paired helical filaments (PHF). This antiserum stains specifically neurofibrillary tangles (NFT) at the light-microscopic level and PHF at the electron-microscopic level in sections of Alzheimer neocortex and hippocampus. We studied the nature of the antigens recognized by this antiserum by immunocytochemistry, immunoblots and immunoadsorption. These approaches showed that the anti-PHF specifically labels a set of low molecular weight 65-50 kDa microtubule-associated proteins, named Tau proteins, which are promoting factors of microtubule assembly. Furthermore, antisera against Tau proteins stained NFT. It is concluded that neurofibrillary tangles are very likely composed of aggregated Tau proteins. This process might be due to an abnormal Tau protein synthesis or to an unknown lesion of certain pyramidal neurons leading to an aggregation of Tau proteins.