PROJECT SUMMARY/ABSTRACT This application is for a Bruker ELEXSYS-II E500 X-band continuous wave (CW) electron paramagnetic resonance (EPR) spectrometer system with temperature control to replace our failing 22-year-old Bruker ELEXSYS E500 instrument. The new Bruker ELEXSYS-II E500 boasts 10-fold greater sensitivity, runs on a solid-state power source, has a digital signal processing unit (SPU), and contains an ultra-low-noise microwave source and a digital rapid field scan module. In all ways, this is a completely advanced version of our obsolete and unreliable system. The importance of this instrument to the success of the multiple NIH-funded and future projects is paramount, and, thus, it is imperative that we have a reliable CW EPR spectrometer. A brand-new Bruker X-band ELEXSYS-II E500 CW EPR spectrometer will replace, and even extend, the capabilities of our current workhorse CW spectrometer in the National Biomedical EPR Center at the Medical College of Wisconsin. Along with increased reliability and stability, the new instrument has significantly improved sensitivity due to modern and improved digital and solid-state parts. In addition, the requested temperature control accessory will extend our capability to maintain accurate sample temperature in the range of 3.8–350 K. This modern technology, which is designed primarily as a research platform for a wide variety of applications such as structural biology, enzyme reactions, redox biology, membrane studies, drug discovery, and technology development, is ideally suited to the specific types of NIH-funded biomedical projects outlined here for a group of 7 Major Users and 7 Minor Users. The Bruker ELEXSYS-II E500 spectrometer is an invaluable asset that will allow us to fulfill our NIH grant obligations and extend our collaborative scientific investigations at MCW and in the surrounding community; it is essential to the continued excellence of our research programs.