Dextromethorphan, its metabolite dextrorphan, phencyclidine, ketamine, MK-801, 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid and DL-2-amino-7-phosphonoheptanoic acid were evaluated for potency to antagonize N-methyl-D-aspartate-induced convulsions following intraperitoneal administration using male CF-1 mice. Whereas reference anticonvulsants (e.g., phenytoin) were ineffective in this model, dextromethorphan and all competitive and noncompetitive N-methyl-D-aspartate antagonists blocked seizures. The results are consistent with the interpretation that dextromethorphan elicits some of its pharmacological responses via an interaction with receptors for excitatory amino acids.