Glutamate and aspartate are excitatory neurotransmitters that have been implicated in a number of pathological states of the nervous system. Accumulation of extracellular excitatory amino acids can be cytotoxic and may also lower the seizure threshold in epilepsy. An important function of the Na(+)-dependent high-affinity excitatory amino acid transporter (EAAT) is the reuptake of secreted amino acid neurotransmitter, possibly maintaining extracellular amino acid concentrations at nontoxic and nonepileptogenic levels. We have isolated the mouse cDNA for EAAT2, a neurotransmitter transporter that shares extensive amino acid sequence homology with one of several previously cloned high-affinity glutamate transporters. The mouse EAAT2 amino acid sequence shares 99 and 97% identity with its rat and human homologues, respectively. It is expressed predominantly in the brain, where it may function as a glia-specific transporter. In an interspecific backcross analysis Eaat2 maps to the central region of mouse chromosome 2, where it is located near quantitative trait loci that modulate neuroexcitability and seizure frequency in mouse models of alcohol withdrawal and epilepsy.