The release of [3H]noradrenaline ([3H]NA) in superfused rat hippocampal synaptosomes was increased concentration dependently by N-methyl-D-aspartate (NMDA). Glycine (1 microM), ineffective on its own, doubled the efficacy of NMDA with no significant change in affinity. The effects of NMDA alone and those of NMDA + glycine were antagonized by D-2-amino-5-phosphonopentanoate (D-AP5), Mg2+, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohept-5,10-imine hydrogen maleate (MK-801) or 7-chloro-kynurenate (7-Cl-KYNA) but not by strychnine. The data provide a direct demonstration of the existence of presynaptic NMDA receptors.