The research programs in multiple laboratories at Scripps have rapidly developed in directions which require extensive hands-on access to a mass spectrometer for widely varying types of experiments. We propose the acquisition of a Thermoquest LCQ quadrapole ion trap mass spectrometer with a MAGIC HPLC attachment to address this critical need. The new instrument will be the cornerstone of a newly established User Access Mass spectrometry facility. This new facility, including the proposed LCQ and a MALDI instrument acquired through other sources, will be supervised by a dedicated Ph.D. level scientist. The supervisor will be responsible for administration of the facility, training of users, and assistance with design and implementation of mass spectrometry experiments. The LCQ will be an indispensible analytical tool for the identification and characterization of proteins, for identification of post-translational modifications, for total chemical synthesis of proteins, for the discovery of small molecule inhibitors of amyloid formation, and for analysis of combinatorial compound libraries. The proposed LC-MS system, with MST capabilities, will provide a wide variety of experimental applications. The SEQUEST software package will be obtained to analyze protein mass spectrometric data and search the protein databases. This equipment will allow separation of proteins and peptides by HPLC, direct analysis of their molecular weight by electrospray mass spectrometry, and in addition, will allow tandem mass spectrometry to obtain sequence information. The direct user-access of this instrument will enable graduate students and postdocs to perform experiments that are beyond what can be achieved in a routine fee-for-service facility. Scientists will be able to tailor MS experiments to their specialized applications, in a format where the experiments can be optimized with direct input from the user. The LCQ LC-MS system should prove to be a powerful research tool that provides critical analytical information to a wide variety of scientists in a wide variety of disciplines.