Preparation techniques for the high resolution scanning electron microscopy of soft biological specimens require extensive improvements to take proper advantage of the increased resolving power of the scanning electron microscopes now available (6 to 3 nm). All preparatory steps, especially metal coating and dehydration or critical point drying need refinement. The grain of metal films must be eliminated or reduced below the limit of resolution of the new scanning electron microscopes. And fine structural details on cell and membrane surfaces must be reinforced by extensive cross-linkage (with bifunctional or photoactivatable reagents) to prevent their microcollapse upon water replacement by media of low dielectric constant. The large number of variables to be checked in developing this new technology and the need for repeated comparisons of SEM to TEM images require a scanning electron microscope of adequate resolving power and high work volume that can be easily shifted from the scanning to the transmission mode of electron microscopy. The JEM- 100 CX provided with a scanning attachment is (without exaggeration) an ideal instrument for the type of developmental work in which we are interested. As adequate preparation procedures will be developed, they will be made available to all the other applicants and their collaborator for investigations concerning the functional morphology of membrane surfaces (distribution and behavior of various receptors and their ligands, distribution of functionally important membrane proteins, e.g., glycophorins, band 3, rhodopsin, etc.) and surface in depth structure of capillaries, especially glomerular capillaries, basement membranes. In addition, this instrument can be provided with attachments for X-ray microanalysis, and used for developing procedures for the localization of chemical elements in situ (beyond their present level of efficiency), and for collecting information re: functionally important ion concentrations within intracellular compartments (endoplasmic reticulum, Golgi complex, secretion granules).