Molecular cloning has elucidated the molecular diversity of the N-methyl-D-aspartate (NMDA)-receptor channel and has provided a solid basis for extensive studies of the structure and function of the NMDA-receptor channel. Mutational analyses have assigned functional domains and the transmembrane topology of the channel subunits. Identification of the multiple subunits with distinct distribution, properties, and regulation has suggested that NMDA-receptor channels are distinct in molecular architecture and functional characteristics in various brain regions at different developmental stages. The physiological significance of the NMDA-receptor channel diversity is presently under investigation by various techniques including gene targeting.