Three excitatory amino acid antagonists, 2-amino-5-phosphonovalerate (APV), gamma-D-glutamylglycine (gamma DGG) and cis-2,3-piperidine dicarboxylate (PDA) have been compared with respect to their ability to block the action of amino acid excitants and both mono- and polysynaptic excitation in the cat spinal cord evoked by stimulation of primary afferent fibres. Each of the three antagonists depressed polysynaptic excitation of dorsal horn neurones. This action correlated with the ability of all of the substances to antagonize responses evoked by N-methyl-D-aspartate (NMDA) and L-aspartate. The order of potency of the antagonists in producing these effects was APV greater than gamma DGG = PDA. PDA (particularly) and gamma DGG also proved to be effective depressants of monosynaptic excitation. This action correlated with the ability of these substances to antagonize quisqualate- and L-glutamate-induced excitation. Antagonism of kainate-induced excitation was usually (but not always) also associated with depression of monosynaptic excitation. These results suggest that, following impulses in low threshold afferent fibres, a transmitter is released from primary afferent terminals which acts at quisqualate- (and possibly kainate-) type receptors and that excitatory interneurones, activated by similar impulses, release a transmitter which acts at NMDA receptors. L-Glutamate and L-aspartate may be the transmitters involved in these monosynaptic and polysynaptic responses, respectively.