The family of metabotropic glutamate receptors (mGluRs) consists of eight homologous G-protein coupled receptors. Several of the mGluRs, including the mGluR4 receptor subtype, are localized presynaptically; activation of this receptor induces an inhibition of neurotransmitter release from nerve terminals. Disruption of the mGluR4 gene in mice results in impaired motor and spatial learning, and alterations in seizure susceptibility. In this study, we have determined the structure of the human mGluR4 gene, as well as its chromosomal localization. A comparison of the gene structure of mGluR4 with the highly homologous mGluR6 receptor subtype reveals that both of the genes contain ten exons with similar exon/intron boundaries. A refined localization of mGluR4 was carried out by constructing a bacterial artificial chromosome clone contig of the region surrounding the gene. Thirteen sequence tagged sites (STSs) were identified within this contig. The gene was localized to chromosome 6 band p21.3 by fluorescence in situ hybridization (FISH). The mapping of the mGluR4 gene indicates that it is approximately 1 megabases centromeric of the major histocompatibility complex and 5 megabase from the GABA(B)R1 gene. The mGluR4 gene also falls within a susceptibility locus for juvenile myoclonic epilepsy suggesting a potential link to this form of epilepsy.