The methods of high resolution electron microscope (HREM) structure analysis will be used to determine the three-dimensional structure of several cell membranes. Consideration of the radiation damage that occurs during microscopy shows that HREM structure analysis is facilitated by the use of specimens that have a two-dimensional crystalline or periodic substructure. Operating within this constraint, we propose to work on a variety of eukaryotic and prokaryotic membranes, and on ordered arrays of peripheral as well as integral membrane proteins. In pursuit of these structural studies we will need to further develop several aspects of HREM structure analysis. We therefore propose to investigate some promising new ideas on the solution of the "hollow cone" problem (3-D reconstruction from a limited angular range of views); we will develop computer software and data management capabilities to extend HREM structure analysis to small, crystalline patches; and we will attempt to extend the structural resolution of which HREM analysis is capable, from the presently proven level of approximately 7 Angstrom units down to the EM instrumental limit of about 3.5 Angstrom units to 4.0 Angstrom units. All work proposed here emphasizes the use of unfixed, unstained, hydrated specimen materials. The proposed work is greatly facilitated by the availability of a low temperature, high resolution stage (which provides a reduced rate of radiation damage); by the use of nuclear track emulsion photographic plates; and by a highly developed facility for microscopy and for data analysis.