Proposed is the acquisition of an intermediate voltage electron microscope which will be equipped for microanalytical X-ray analysis, T.V. camera imaging and direct video output for computer image storage, processing, and analysis. The instrument will be incorporated into the electron microscopy laboratory maintained as an institutional resource by the Department of Pathology. As a resource, the instrument will be used by investigators from throughout Bowman Gray School of Medicine and Wake Forest University. This orientation is reflected in research projects involving investigators from 6 academic projects. In addition to the 6 core projects, 11 supplemental projects from 5 other departments at Bowman Gray School of Medicine and one project describing studies at the University of North Carolina are listed to document breadth of applicable research and potential for regional orientation. The six core projects describe experiments which capitalize on the unique characteristics of increased beam penetration and greater resolution with thick sections and whole-mount preparations. These characteristics will enhance studies of cellular events such as lysosome organization, surface receptor location, host cell- parasite interactions, cytoskeletal superstructure, and cell/matrix interactions in tissues. A major feature of the core projects is the unique correlative and often multiple use of 3-D microscopy, image processing/reconstruction, cytochemistry, immunocytochemistry, and microanalysis enabling better understanding of spatial questions relating cell and tissue organization to biochemistry, function and pathobiology.