Apoptosis is a programmed cell death that occurs during the development of the nervous system and in neurodegenerative disorders. Tau protein is a cytoskeletal component that promotes microtubule polymerization and stabilization. Apoptosis was induced in primary neuronal cultures by a prolonged exposure (16 h) to the NMDA (N-methyl-D-aspartate 20 microM) or by serum deprivation. The percentages of apoptotic neurons expressing phosphorylated tau (AT8) immunoreactivity are comparable in control and NMDA-exposed cultures (7.5 +/- 1.9 and 6.9 +/- 1.9%, respectively). At the opposite, the percentage of apoptotic neurons expressing de-phosphorylated tau (tau 1) immunolabelings is dramatically increased in NMDA-treated cultures (X 2.3 of controls). Similar results were also observed 48 h after serum deprivation. These results demonstrate in vitro that under these conditions, resistant and sensitive cortical neurons to apoptosis can be partly differentiated according to their phosphorylated tau immunoreactivities.