The present study examined in urethane-chloralose anaesthetized rats whether N-methyl-D-aspartate (NMDA) is involved in the depressant effect of flupirtine on the monosynaptic Hoffmann (H)-reflex recorded from plantar foot muscles and on polysynaptic flexor reflexes recorded from tibialis muscle. Intrathecal administration of both the specific NMDA antagonist (-)-2-amino-7-phosphonoheptanoate and of flupirtine depressed the polysynaptic flexor reflex without affecting the monosynaptic H-reflex. In contrast, the non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione depressed the H-reflex without affecting the flexor reflex. The depressant effect of flupirtine on the flexor reflex was prevented by co-administration of NMDA, but not by co-administration of the non-NMDA agonist alpha-amino-3-hydroxy-5-tertbutyl-4-isoxazolepropionic acid. These observations suggest that NMDA might be involved in the action of flupirtine.