The NMDA subtype of ionotropic glutamate receptors has been implicated in the activity-dependent modification of synaptic efficacy in the mammalian brain. Here we describe a cDNA isolated from Drosophila melanogaster which encodes a putative invertebrate NMDA receptor protein (DNMDAR-I). The deduced amino acid sequence of DNMDAR-I displays 46% amino acid identity to the rat NMDAR1 polypeptide and shows significant homology (16-23%) to other vertebrate and invertebrate glutamate receptor proteins. The DNMDAR-I gene maps to position 83AB of chromosome 3R and is highly expressed in the head of adult flies. Our data indicate that the NMDA subtype of glutamate receptors evolved early during phylogeny and suggest the existence of activity-dependent synaptic plasticity in the insect brain.