The feeding behaviour of the freshwater polyp Hydra vulgaris (Cnidaria, Hydrozoa) is modulated by a number of molecules acting as neurotransmitters in other nervous systems. Here we present biochemical and functional evidence of the occurrence of putative NMDA receptors in Hydra tissues. Saturation experiments showed the presence of one population of binding sites with nanomolar affinity and low capacity for [3H]MK-801. Before equilibrium, [3H]MK-801 binding was increased by the agonists glutamate and glycine as well as by reduced glutathione (GSH). In vivo the glutamate receptor agonist NMDA markedly decreased the duration of the response to GSH. This effect was linearly related to ligand doses in the nanomolar concentration range and was counteracted by either the NMDAR-specific antagonist D-AP5 or by the d-serine antagonist DCKA. When NMDA concentration was increased to 10 or 100 µm, duration of the response to GSH was no longer affected unless the lectin concanavalin A, which prevents receptor desensitization in other systems, was added to the test medium. Simultaneous administration of ineffective doses of NMDA and strychnine, glycine or d-serine, an agonist at the glycine binding site of the NMDA receptor in vertebrate CNS, resulted in a strong reduction of response duration. Both D-AP5 and DCKA suppressed this effect. These results, together with the decrease in response duration produced by d-serine, support the hypothesis that NMDA-like glutamate receptors may occur in Hydra tissues where they are involved in modulation of the response to GSH with opposite actions to those of GABA and glycine.