The Massachusetts Institute of Technology proposes that support for the High Field NMR Resource (Grant no. RR00995-13), located at the Francis Bitter National Magnet Laboratory (FBNML), be continued for five years and that its scope be enlarged to support ongoing activities in in-vivo spectroscopy and imaging of animal models and human subjects at the M.I.T. MRI Facility. We thus propose to create and operate a new entity called the Comprehensive NMR Center for Biomedical Research. This center will be comprised of two division; (1) the existing High Field NMR Resource, now in its 13th year of operation, and (2) the In-vivo MNR/MRI Facility, a research laboratory developed in parallel during the past six years at M.I.T. almost exclusively with private funds. The major new technologies which we propose to introduce are: (1) a capability to perform high-resolution 3D-NMR: (2) an enhanced capability for NMR microscopic imaging and spectroscopy; (3) the use of M.I.T.'s unique actively shielded pulsed gradient coils for NMR microscopy and in- vivo spectroscopy and imaging; (4) a high performance spectrometer for dynamic nuclear polarization studies of crystalline proteins; (5) a high- resolution multinuclear 600 MHz spectrometer; (6) a whole body human in- vivo spectroscopy/imaging system utilizing a 1.5T/120 cm magnet of our own design and construction; (7) enhanced computer facilities for acquisition, data processing and display of 2D- and 3D-NMR data sets and for in-vivo spectroscopy and imaging. Our objective during the next five years is to establish an integrated, comprehensive capability which will allow study by NMR of all the diverse biological systems -- macro-molecules, subcellular organelles, microorganisms, cells, mammalian tissues, intact organs, animals and humans. Experimental capabilities will exist for NMR microscopy, NMR spectroscopy (solutions, solids, in-vivo tissues) and NMR imaging. The comprehensive nature of the Center will allow for research projects initiated at the High Field NMR Division to migrate naturally to the In- Vivo MRS/MRI Division. Thus, a given project begun at the cellular or small animal level can be easily broadened in scope to include investigations of larger animals and humans. Such advanced NMR capabilities, which permit long-term, in-depth, health-related investigations and to which researchers have ready, equitable access do not exist at a single site in the greater Boston/Cambridge area.