Glutamate toxicity has been involved in the pathophysiology of a large variety of neurodegenerative disorders. Tau Protein is a micro-tubule-associated protein that promotes microtubule polymerization and stabilization. Phosphorylated tau protein accumulates in paired helical neurofilaments, the major constituent of neurofibrillary tangles observed in the brain of patients suffering from Alzheimer disease (AD). In this study, using confocal laser microscopy and immunoblot analysis, we report that acute (500 mu M for 15 min) or chronic (20 mu M for 16 h) N-methyl-D-aspartate (NMDA) neuronal toxicities modify the immunoreactivity of phosphorylated tau. Neuronal degeneration produced by N-methyl-D-aspartate is associated with an augmented immunolabeling of phosphorylated tau proteins at serine 202 (AT8 antibody) as observed in paired helical neurofilaments. This finding could help to determine the cellular mechanisms at the origin of neuronal degeneration associated with modifications of phosphorylated tau immunoreactivity produced by receptor-mediated extracellular signals.