Structural studies on biological macromolecules and macromolecular assemblies have been performed by high resolution electron microscopy complemented by optical diffraction and digital image processing. Micrographs of human immunoglobulin IgG crystals have been analyzed extensively to determine their structural fidelity. Compared to reference images derived from X-ray crystallography, the computer-optimized micrographs show excellent fidelity to 2nm resolution and a predominantly non-specific distribution of the uranyl stain. The capsid structure of bacteriophage T7 has been solved by processing micrographs of polycapsids, tubular foldings of the viral surface lattice, thereby resolving hexamers of the major capsid protein, gp10. These results have been developed into subunit packing schemes for the tubes, as well as for the icosahedral wild-type capsid. Direct mass measurements of fibroblastic intermediate filaments have been effected by image analysis of scanning transmission electon micrographs: these findings have established the efficacy of the in vitro assembly reaction and imposed a stringent constraint on feasible geometries for the arrangement of fibrous subunits within these filaments.