The GM/CA Macromolecular Crystallography (MX) Core has three main goals. We will provide a modern, powerful environment for sample screening, fine sample examination via rastering, and data collection in fixed-energy, SAD and MAD modes for single- or multi-crystal samples. GM/CA will create an intuitive, sophisticated, biologist-friendly user interface for beamline control and data processing and analysis for both on-site and remote users. We will implement beamline and software upgrades for optimal user operations in order to take advantage of the upgraded APS source (APS-U), which will be realized within this funding period. GM/CA Group Leader Dr. Robert Fischetti leads the MX Core, Dr. Craig Ogata (Operations Section Lead) leads the user program, and Dr. Sergey Stepanov (Controls Section Lead) leads the computing and networking effort. Beamlines 23ID-B and 23ID-D will be similarly configured with high-quality X-ray beams, instruments and software for diffraction experiments at user-selectable wavelengths with a beam of user-selectable size to enable macromolecular crystallography of challenging biomedical problems. GM/CA will provide powerful, user-friendly control software and a safe environment on the experimental floor for user experiments based on peer-reviewed applications for beam time. We will complete a project to upgrade aging beamline optics and to increase the flux of the 5-?m, 10-?m and 20-?m beams by focusing. With the upgraded optics, we will provide a beam down to 1-?m diameter for the APS-U source and will implement an improved endstation for accurate sample visualization and positioning, a scheme for rapid beam size changes between 1 ?m and 20 ?m, an upgraded user interface for rapid sample scanning and data collection, and integration of data analysis software to process multi-crystal datasets. We will test a variety of serial crystallography methods in order to provide this capability to users at the start of APS-U. We will continue a multi-tiered maintenance program to anticipate problems ahead of failures and provide full beamline capabilities to users for all scheduled beam time.