Neuronal apoptosis a hallmark of brain development could also be involved in neurodegenerative diseases. Glutamate toxicity is widely proposed as an important factor in the pathogenesis of neurological disorders. We show here that, in rat primary cortical cultures, the blockade of N-methyl-D-aspartate (NMDA) glutamate receptors exacerbated neuronal apoptosis induced by serum deprivation. This effect is observed at early stage of cultures (9 days in vitro (DIV)) and mildly decreases in more mature cultures (13 and 15 DIV). At the opposite, low concentrations of NMDA (5 microM) or glutamate (5 microM) prevented the neuronal apoptosis induced by trophic support withdrawal. In primary cortical cultures, the proapoptotic effect of trophic support removal can be modulated by NMDA receptors depending upon the magnitude of these glutamate receptor activation.