Based on analysis of aligned amino acid sequences the following statements are made: (i) There is evolutionary homology between the N-terminal extracellular region of ionotropic Glutamate receptors/Kainate Binding Proteins and a family of procaryote amino acid binding proteins. (ii) Homology of the N-terminal extracellular domain of the metabotropic glutamate receptors with a family of receptors with a guanylate cyclase intracellular domain appears to be valid. (iii) There is no evidence for homology between the N-terminal extracellular domain of the nicotinic Acetylcholine, GABA, Glycine and 5HT3 receptors and that of the ionotropic Glutamate receptors/Kainate Binding proteins. (iv) The proposal of homology for the N-terminal extracellular domain of metabotropic Glutamate receptors and that of ionotropic Glutamate receptors does not appear to hold.