The effect of recombinant brain-derived neurotrophic factor (BDNF) on cultured rat cortical neurons was examined. Brief exposure of cortical neurons to glutamate followed by incubation with glutamate-free medium reduced cell viability by 60-70% when compared with the control value. Simultaneous addition of recombinant BDNF to rat cortical cultures with glutamate did not affect this reduction of cell viability. However, 24 h pretreatment of rat cortical cultures with recombinant BDNF resulted in a significant reduction of glutamate-induced neuronal damage. These findings suggest that BDNF can protect cortical neurons against glutamate-induced neurotoxicity.