The purpose of the proposed grant is to assist in the purchase of a state- of-the-art, field emission electron microscope for the study of macromolecular structures. This microscope is to be the centerpiece of a new initiative in structural biology at Yale School of Medicine. Yale has a distinguished history in the determination of macromolecular structures by X-ray diffraction, and also a distinguished history in the use of electron microscopy in cell biology. Until now there have been no facilities for cryo-electronmicroscopy of macromolecular assemblies, an approach that bridges the two areas. We propose the purchase of a Philips Tecnai F20 transmission electron microscope with accessories for lowdose imaging of cryogenically cooled specimens. This field-emission microscope will be used for structure determination of membrane proteins in two-dimensional crystals, and for three-dimensional reconstruction of macromolecular structures using single-particle techniques.