Systemic administration of monosialoganglioside GM1 is efficacious in reducing excitatory amino acid (EAA)-related neurotoxicity in vivo following intracerebroventricular injection of N-methyl-D-aspartate (NMDA) in 7-day-old rats. Five days later, NMDA-treated animals showed extensive brain damage which was accompanied by significant decreases in brain weight, choline acetyltransferase activity and 3H-ouabain binding. All these neurotoxic effects were significantly reduced with ganglioside treatment. Since excessive activation of EAAS is implicated in hypoxic-ischemic brain damage, these results favor the hypothesis that a similar effect is involved in the ability of ganglioside to ameliorate outcome following cerebral ischemia.