ABSTRACT NSF support is requested for the purchase of a 600 MHz NMR spectrometer for high resolution structural studies of biological macromolecules at Yale University. Studies of macromolecular structure and function using high-resolution solution NMR has become a major activity for research groups in the Departments of MB&B and Chemistry at Yale. The research described below focuses on fundamental questions in structural biology and biochemistry involving metalloproteins (J. Coleman, L. Regan and J. Caradonna), proteins and protein-protein interactions (J. Prestegard and L. Regan), RNA (D. Crothers and P. Moore), membrane proteins (D. Engelman and S. Smith) and the collection of datasets of proteins and RNA for methodological developments (A. Brunger). Currently, this research is pursued on two 500 MHz NMR spectrometers. The plan is to acquire a 600 MHz spectrometer to complement the existing 500 MHz instrumentation. The 600 MHz instrument will provide important and substantial improvements in sensitivity, resolution and spectrometer time available. The projects of the nine research groups described below all have components that would benefit markedly from the higher magnetic field.