This proposal requests funds to support the acquisition of a modern, high performance intermediate voltage transmission electron microscope (IVEM) to replace an aging Japanese Electron Optics (JEOL) JEM- 4000EX that has served as a production instrument for automated 3D imaging of thick sections (electron tomography, electron optical sectioning) for nearly 17 years. This instrument will physically supplant the JEM-4000EX at the National Center for Microscopy and Imaging Research (NCMIR) on the campus of the University of California, San Diego. The NCMIR is an NCRR/NIH Biomedical Technology Research Center established in 1989 to develop computer-aided advanced microscopy for acquisition of structural and functional data in the dimensional range of 1 nm3 to 100 um3, a dimensional range referred to as the """"""""meso"""""""" or middle scales. This instrument will serve the primary function of enabling the continued support of an increasing base of driving application projects that require tailored performance and functionality in the area of meso-scale, 3D imaging of thick, 1 to 3 um sections of cells and biological tissues. ? ? ?