N-Methyl-D-aspartate (NMDA) produced a concentration-related increase in [3H]noradrenaline release from adult rat cervical spinal cord slices. Its potency was relatively low and the response concentrated in dorsal spinal regions although also observed in ventral slices. NMDA did not increase the release of radiolabelled glutamate, aspartate, gamma-aminobutyric acid (GABA), acetylcholine or serotonin. In comparison with previously characterised NMDA responses in the striatum, (release of dopamine, GABA, acetylcholine or spermidine) the spinal response was particularly sensitive to MK-801 and magnesium and to L-689,560 but not to other glycine receptor antagonists (7-chlorokynurenate, CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), DNQX (6,7-dichloroquinoxaline-2,3-dione), (+)-HA966). Dextrorphan and dextromethorphan produced partial or biphasic inhibition curves suggesting a subdivision of NMDA receptors. NMDA-evoked [3H]noradrenaline release was moderately sensitive to CPP and CGP37849 but insensitive to arcaine. These characteristics distinguish the native spinal NMDA receptor subtype(s) from those so far characterised in the striatum suggesting a unique spinal NMDA receptor subtype.