By electron microscopy of single molecules size and shape of large aggregates can be visualized. Subunits may be identified by the generation and analysis of defined fragments or by specific labelling. This information combined with high resolution crystal structure determination of the subunits allows a reliable reconstruction of the large assemblies in atomic detail. When well-ordered two-dimensional preparations are available, substantially improved resolution can be obtained by electron microscopy and molecular details recognized. A direct comparison is then possible with crystal structures and structural differences be defined i.e. of membrane bound and three-dimensional crystalline species. A new development of crystal decoration and pattern analysis by electron microscopy allows to identify molecules in crystal
lattices and determine their orientation and location. This information provides a starting point for the structure determination by x-ray crystallography.