Monosialoganglioside (GM1) has been considered to have a neurotrophic factor-like activity. Nerve growth factor (NGF), a member of the neurotrophin family, is essential for neuronal survival, differentiation and maturation. The aim of the present study was to investigate whether co-administration of GM1 and NGF reverses glutamate (Glu) neurotoxicity in primary cultured rat embryonic dorsal root ganglion (DRG) neurons. DRG neurons were exposed to Glu (2 mmol/1), Glu (2 mmol/1) plus GM1 (10 microg/ml), Glu (2 mmol/l) plus NGF (10 ng/ml), Glu (2 mmol/l) plus GM1 (5 microg/ml) and NGF (5 ng/ml) and then processed for detecting intracellular concentrations of Ca2+ ([Ca2+] i) by confocal laser scanning microscopy and growth-associated protein 43 (GAP43) mRNA by RT-PCR. The fluorescent intensity in Glu plus GM1 and NGF incubated neurons was the lowest as compared with that in other groups. The expression of GAP43 mRNA in Glu plus GM1 and NGF incubated neurons was the highest as compared with that in other groups. These results implicated that GM1 and NGF have synergistic neuroprotective effects on DRG neurons with excitotoxicity induced by Glu in vitro.