This application is for the acquisition of a continuous flow gas chromatograph combustion/ paralysis-isotope ratio mass spectrometer (GC-CF-IRMS) with modules for the on-line assay of low enrichments of compounds labeled with 13C, 15N, 18O, and 2H. The applicants are five established and two junior faculties of Case Western Reserve University and two colleagues from Youngstown State University (Ohio) and the University of Oklahoma, all with expertise in gas chromatography-mass spectrometry. The instrument will be used for basic science and clinical investigations on enzymatic reaction mechanisms, gluconeogenesis, lipogenesis, ketone body metabolism, protein metabolism, fatty acid oxidation, and inborn metabolic disorders. No such instrument is presently available at CWRU or in Greater Cleveland. The instrument will be set up in the Center for Metabolic Mass Spectrometry of the Department of Nutrition of CWRU. It will be made available to all scientists of the Cleveland area. The costs of operating and maintaining the instrument will be shared by the users. The availability of this instrument will considerably increase the scope of the basic science and clinical investigations conducted by the applicants.