Recent technical advances have transformed conventional transmission electron microscopy into an analytical tool for detecting and quantifying a variety of signals produced by a high voltage electron beam striking a specimen. It is now possible to obtain accurate reproducible information characterizing the elemental nature of individual intracellular particles and to determine the molecular composition of fibrous elements and matrices within the cell. We can now detect the concentrations of individual elements within organelles and changes in the membrane composition resultant from normal developmental processes, pathological states and/or the application of drugs. The amalgamation of analytical electron microscopy and high resolution transmission microscopy affords new opportunities currently unavailable in the departments of Anatomy, Pharmacology and Neurology. This application has two purposes: (1) The replacement of an aging Philips EM300 transmission electron microscope for which parts may no longer be available and which is experiencing ever increasing down time. (2) This replacement will provide an ultrahigh vacuum instrument designed to meet a wide range of current research needs in high resolution ultrastructural studies as well as providing the capability for extension to a full range of analytical work including cryotransfer and x-ray analysis of small volumes found in thin specimens. Although other high resolution electron microscopes are available on the medical school campus, none are equipped with an x-ray analyzer or microprobe apparatus. Those on campus are generally heavily used and available only on an ad hoc emergency basis. The Philips EM420T microscope has been selected to meet our present varied requirements and to allow maximum future expansion as our needs and technologies develop. Future expansion is envisioned to include a STEM computer interface, high resolution super twin objective lens system with signal mixing display facility and an EELS (electron energy loss spectrometer). The Philips EM420T analytical electron microscope will provide the focus of an electron optical facility (ultrastructure and microprobe electron optical laboratory) for researchers in the Departments of Anatomy, Pharmacology, and Neurology of Rutgers Medical School.