Duke University will purchase a cryogenically-cooled, ultra-high sensitivity triple resonance, 1H{13C115N}, 5 mm probe and associated closed-cycle cryogenic system for the Varian Inova 800 MHz nuclear magnetic resonance (NMR) system currently operating in its NMR Center. Cryogenically cooling an NMR probe and the associated pre-amplifier hardware has been demonstrated to provide a significant improvement in achievable signal-to-noise ratios in studies involving both samples of biologically important macromolecules at millimolar and micromolar concentrations and of small molecule metabolites at nanomolar concentrations. Developments in NMR instrumentation, NMR experimentation and molecular biology have provided researchers with the ability to investigate more challenging and, by extension, more biomedically relevant systems involving large monomers and complexes, macromolecules with limited solubility, biomolecules under conditions that mimic those encountered in-vivo, metabolites at very low concentrations and the dynamics of systems over a wide range of timescales. Currently, the 800 MHz system, located in the Duke University NMR Center, is utilized by a large contingent of scientists, both within the Duke community and across the Southeast region, to address a broad range of biologically significant projects. Seven investigators in Biochemistry and the NMR Center at Duke, along with nine scientists from the University of North Carolina, North Carolina State University, the University of Virginia, the NIEHS and St. Jude Children's Hospital constitute the initial majors users of the cryogenically-cooled probe. All of these investigators are currently involved in technically demanding research aimed at elucidating the structure, function and dynamics of important biomedical and biological macromolecules. The need for even higher sensitivity than currently offered by conventional probes has been expressed by many of these groups as they extend their research to more technically demanding problems. The addition of an ultra-high sensitivity cryogenically cooled probe to the 800 MHz spectrometer in the Duke NMR Center represents a major advance to a unique resource in the region: an addition that will enhance an already vibrant research community.