An accurate depiction of cytoplasmic structure is critical for understanding the basic properties of cells, such as maintenance of shape, polarity, motility and intracellular transport. In addition, macromolecular structural associations between cytoplasmic components, such as the cytoskeleton and the ground substance (the medium in which cellular components are suspended), may be important for defining the environmental background for metabolic processes. Central to this is the question of whether cytoplasmic enzymes involved in metabolic processes are freely soluble and randomly distributed within the cytoplasm of a living cell or are in a bound and therefore structured state. The composition and organization of the ground substance and how it relates to the cytoskeleton has been the focus of a number of ultrastructural studies of cell cytoplasm in the last ten years. These studies have now stimulated further investigation of cytoplasmic structure using a variety of electron microscopic techniques.