We have isolated clones from a human brain cDNA library coding for two splice variants of mGluR1. The combined sequences account for 6864 base pairs (bp) of the approximately 7 kilobase (kb) transcript seen on northern blots of human brain mRNA. The distribution of mGluR1 mRNA in human brain is similar to that found in rat brain and the gene for mGluR1 is localized on human chromosome 6. The mRNA for mGluR1 alpha contains an open reading frame that codes for a 1194 amino acid protein, which is slightly smaller than rat mGluR1 alpha. The major structural difference noted between the human and rat mGluR1 is a deletion of 21 nucleotides which would result in the loss of seven amino acids in the middle of a proline- and glutamine-rich region of the C-terminal tail of mGluR1 alpha. The 85 bp exon that results in the HmGluR1 beta splice variant was found to code for a protein with two amino acid differences compared to the rat receptor. Functional and pharmacological characterization of heterologously expressed human mGluR1 was performed using electrophysiological recordings from Xenopus oocytes and calcium imaging in HEK-293 cells. No major differences were found in the response of human mGluR1 to typical agonists and antagonists compared to the rat, or in the behavior of the two splice variants.