The neuronal microtubule-associated phosphoprotein, tau, has been identified as a major antigenic component of paired helical filaments in Alzheimer's disease (AD). The extent and distribution of altered tau antigens in AD brain, other than those found in neurofibrillary tangles (NFT) and senile plaque (SP) neurites, has not been widely discussed. We have examined tau immunoreactivity in AD using the monoclonal antibody (MAb), 5E2, raised against human fetal tau. Four types of abnormalities were recognized by MAb 5E2, each having some counterpart in Bielschowsky silver impregnations: 1) NFT; 2) thickened neurites in SP; 3) diffuse perikaryal staining seen in some neurons apparently lacking NFT; and 4) a dispersed network of randomly oriented thickened neurites not clustered into discrete plaques but found in NFT- and SP-rich cerebral cortex. These four alterations could also be recognized using three different polyclonal antibodies which had strong tau immunoreactivity but were optimally shown by MAb 5E2. Our findings demonstrate the complexity of altered tau-immunoreactive neuronal elements and emphasize the widespread abnormality of microtubule-associated proteins in AD cortex.