On the basis largely of neuropharmacological analysis, three different receptors mediating neuronal excitation can be identified. The first is activated by quisqualate and other "flexible" molecules including L-glutamate and appears to bind its ligands in a folded configuration. The second is excited by NMDA and has a more extended conformation, the spacing between the amino and the omega-carboxylate groups being the determinant of specificity. The third type accepts kainate and appears to possess a reactive site for the unsaturated side chain which is essential to the operation of this receptor. All three classes appear to be implicated in synaptic events [although some kainate receptors at least are certainly extra-synaptic (Watkins et al., 1981)] and each appears to activate different ionophores in neuronal membranes. Of the endogenous amino acids which may function as synaptic transmitters, L-glutamate and L-cysteate seem to react preferentially with quisqualate receptors (McLennan and Lodge, 1979), while L-aspartate is more of a mixed agonist capable of reaction both with quisqualate and with the NMDA types. Whether folate has a physiological role involving kainate receptors is unknown; and the same is true of any action possessed by quinolinate. The fact that there are amino acid excitants which are pharmacologically distinct from those reacting with any of the three best known receptors suggests that at least one more class of receptor may also exist, but no further information is available at the present time. Other sites with which the pharmacologically active acidic amino acids react are identifiable neurochemically in membrane preparations derived from tissues of the central nervous system. Kinetic studies and analysis of inhibition of sodium-independent binding indicate that there are sites which accept glutamate, others binding aspartate and a third which binds kainate. However, the first does not correspond completely to the quisqualate excitatory receptor, and NMDA does not react with any of the binding sites. It is difficult to conclude then that any of these binding sites can be fully identified with the excitatory receptors. Finally, there are a number of systems which in their patterns of activity again appear completely distinct, but which presumably mediate uptake of amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)