The specific aim of this proposal is to purchase an area detector for macromolecular X-ray crystallography. The instrument would be installed on a rotating anode X-ray generator in the Principal Investigator's laboratory. We prefer the configuration based on a Rigaku R-AXIS II imaging plate system because it appears to be the most cost-effective system that is available at the time of this writing. The University of Pittsburgh will support this project by: Allocating $40,000 to be used as a cost sharing contribution towards the purchase of the instrument; $20,000 towards the maintenance of the equipment in the second and third years of operation (including purchase of a service contract) and half the cost of a service contract in the fourth and subsequent years (up to a limit of $8,000). This proposal is motivated by an accelerating pace of structural work in Pittsburgh that has outstripped the capacity of our existing data collection equipment. Six projects, independently funded by the NIH, currently have a total of 35 different crystal forms ready for data collection. Fourteen of these forms require screening for isomorphous derivatives while in nineteen cases only the native data need to be collected. These projects are: """"""""Structure-Function Relationships of RNA Polymerases"""""""", """"""""Structure-Function of Neurophysin-Hormone Systems"""""""", """"""""StructureFunction Relationship in Glutamine Binding Protein of Escherichia coli"""""""", """"""""Structure Characterization of Liver Aldehyde Dehydrogenase"""""""", """"""""Structural Investigations of Mode of Action of Drugs"""""""" and """"""""Structure and Function of EcoRI Endonuclease"""""""".