The objective of this project was to explore the essential requirements for purifying recombinant and endogenous forms of the metabotropic glutamate receptors (mGluRs) for analysis by mass spectrometry. Truncated c-myc mGluR4 secreted from transfected human embryonic 293 kidney cells was purified by immunoprecipitation using a c-myc-specific affinity conjugate. The purified receptor was analyzed by gel electrophoresis, subjected to in-gel digestion with trypsin, and analyzed by MALDI-TOF and liquid chromatography tandem mass spectrometry. Using this method, the amino acid sequences of three peptides were found and matched correctly to the truncated mGluR4 receptor. Attempts were made to purify the endogenous mGluR4 from rat cerebella using immunoprecipitation with mGluR4-specific antibodies as well as hydroxyapatite and ion exchange chromatography. MALDI-TOF and tandem mass spectrometry could not identify the endogenous mGluR4 partially purified by anion exchange chromatography. My results indicated that protein purification is crucial to the successful analysis of mGluRs using mass spectrometry.