The dicarboxylic amino acids L-glutamate and L-aspartate are likely to be the excitatory transmitters released at the majority of synapses in the mammalian central nervous system (CNS) (Fonnum et af . , 1983). The finding that, under appropriate experimental conditions, these substances can destroy neurons, producing a characteristic ‘axon-sparing’ lesion (Olney, 1983), is therefore of enormous potential significance. The term ‘excitotoxin’ was introduced by Olney (1974), and arose from the observation that the severity of the toxic response to excitatory amino acid receptor agonists was directly proportional to their excitatory potencies on central neurons. A number of excitatory analogues of glutamate or aspartate, such as kainate, quisqualate and ibotenate which are derived from natural product sources, exhibit powerful excitotoxic effects when injected locally into the CNS. These agents have thus found wide usage as experimental tools in neuroscience research. The precise mechanisms underlying the production of excitotoxicity are still poorly understood, and although there is presumably a final common pathway involving massive entry of calcium ions and associated activation of proteases, followed by structural collapse of the cell, there appears to be no unifying mechanism applicable to each of the excitotoxins. Indeed, there are substantial differences between the individual excitotoxins with regard to the susceptibility of individual brain areas. This might be attributable to a variety of factors, including (i) the requirement in certain cases of an intact excitatory innervation, (ii) ‘distant’ damage not related to direct local effects, but dependent upon convulsive activity (characteristic of kainate toxicity), and (iii) the interaction of the excitotoxins with different populations of excitatory amino acid receptor, the distribution of which may vary considerably between brain areas. In the past, a receptor definition was arrived at on the basis of the preferential actions of the excitatory agonists N-methyl-D-aspartate (NMDA), quisqualate and kainate (Watkins & Evans, 1981). While a useful working system, it relates nothing regarding the function of these receptors, where, in particular, the transmitter L-glutamate is an effective agonist at each site. Similarly, quisqualate and kainate do not show absolute selectivity. A fourth type of receptor site has also been suggested to exist, where ~-2-amino-4phosphonobutyrate (APB) is an agonist and potently antagonizes synaptic responses at a number of identified acidic amino acid synapses in the CNS (Foster & Fagg, 1984). It appears that this site may be presynaptic in location, serving to inhibit transmitter release (Butcher et al., 1986). Its possible identity with the proposed glutamate autoreceptor (McBean & Roberts, 1981) remains to be resolved. Substantial effort has been directed into the use of binding studies, particularly with ~-[’H]glutamate, within recent years, and considerable confusion has arisen (Roberts, 1983). One of the major problems has been the later discovery that in the presence of CI , L-glutamate labels a dominant population of sites that is sensitive to APB, quisqualate and a number of other L-isomers of excitatory amino acids and antagonists. This site, which can also be labelled using DL-[’H]APB (Butcher et al., 1983), cannot readily be related to any of