Several recent studies have demonstrated that the ultrastructure of the plasma membranes at certain regions of cell-to-cell contact can be different from the structure of the general plasma membrane. When the surface specialization of one cell is matched by the surface specialization of an adjacent cell, then these regions are called cell-to-cell junctions, or simply cell junctions. Data have accumulated on the classification, ultrastructure, and physiology of cell junctions and now several correlations of structure with function have been put forward as working hypotheses. Current concepts of the structure of cell junctions have evolved rapidly on the basis of observations from many laboratories so that many names have been applied to cell junctions. Therefore, a brief review of terminology and its origins is necessary for clarification of the relationship between recent studies and those in the older literature. Also for those readers who are unfamiliar with current electron microscopic preparative techniques, a brief review of pertinent aspects is included in section II. Light microscopists stressed the importance of regions of contact between cells but were limited to a few basic observations by the low resolution of the light microscope. They noted that a circumferential refractile ring, called the terminal bar, is present in many columnar epithelial cells at the apical portion of the cell-to-cell apposition. It was presumed that these terminal bars sealed adjacent cells to each other, thus allowing cells to form a coherent tissue barrier. In stratified squamous epithelia, light microscopists noted small dense bodies at regions of cell-to-cell contact. They named these dense bodies" desmosomes" or" intercellular bridges". Some observers suggested that there might be continuity of the cytoplasm of adjacent cells at desmosomes (reviewed by Fawcett, 1958; Wood, 1959; Fawcett, 1961). With the introduction of biological electron microscopy, individual cells in epithelia were found to be enclosed by a continuous plasma membrane. The plasma membrane appeared trilaminar, ie composed of two 25/~ electron-dense laminae separated by a 30 A electronlucent lamina (Fig. l). This appearance was termed the" unit" membrane and was interpreted according to the Davson-Danielli model of membrane structure (Robertson, 1959, 1960). The continuity of this membrane around the cell perimeter dispelled ideas of cytoplasmic continuity between adjacent cells for many years (Fawcett, 1958, 1961). In nonjunctional regions, adjacent cell membranes were usually separated by a 200 to 300 A interspace. By electron microscopy, desmosomes were found to contain paired dense cytoplasmic plaques which abut on the plasma membrane of adjacent cells that are separated by a 300 to 350/k interspace (Porter, 1954). The refractile ring called the terminal bar was noted to be formed by three types of junctions (cf. Yamada, 1955; Farquhar and Palate, 1963), one of which was the desmosome. Another junction in the terminal bar resembled the desmosome in having a similar separation of the apposed membranes but had cytoplasmic plaques of 47