The Electron Microscopy Center at the Indiana University School of Medicine has an urgent need for a LEICA EM PACT High Pressure Freezing (HPF) and Processing System. The HPF rapidly freezes microbiopsies, tissue pieces or cultured cells at a rate of >13,000 degrees/second. The automated freeze substitution processor allows these specimens to be uniformly processed. This system represents the newest approach to processing tissues for electron microscopy (EM) without chemical fixation. The EM Center is a multi-user facility dedicated to research and a Research Core Laboratory for the Indiana University School of Medicine. The EM Center has served the research needs of IU investigators since 1961 with strong School and Departmental support for its research contributions. The EM Center has a full-time faculty Director, Dr. Gattone, a full-time manager, Ms Miller, and is available to all IU School of Medicine investigators. The present application is for the Leica High Pressure Freezer and Processing System because of a need by eight, NIH funded investigators. Most investigators need this system to perform immunocytochemistry for fixation sensitive antigens or to avoid potential artifacts due to chemical fixation. However, some projects have very innovative needs, such as Dr. Molitoris' use of the Leica needle microbiopsy system, for samples taken from a rat kidney while viewing it, in vivo, with a two photon confocal microscope. Dr. Evan needs to freeze samples obtained directly from the operating room (OR). The mobility of the Leica HPF allows the unit to be easily transported to the pathology room by the OR or two-photon confocal microscope suite. Two highly qualified EM Specialist, Ms. Miller and Pennington, have expertise in the use and maintenance of this Leica freezing and processing system. The research and physical environment, EM Center personnel and IU School of Medicine institutional support make the IU EM Center an excellent place for the appropriate use of the Leica HPF and Processor System.