By testing the effect of spermine on N-methyl-D-aspartate (NMDA)-evoked [3H]noradrenaline release in rat hippocampal slices, we revealed a presynaptic spermine-sensitive NMDA receptor most probably localized on noradrenergic terminals. Spermine (1 mM), per se totally inactive, was able to reverse the tetrodotoxin-induced blockade of the NMDA effect, restoring tritium efflux to approximately 50% of the NMDA-evoked release measured in the absence of tetrodotoxin. This effect was partially antagonized by D(-)-2-amino-7-phosphonoheptanoic acid. Our results may help to elucidate the role that spermine exerts on excitatory amino acids receptors.