In recent years, it has become possible to investigate the cell surface of normal and tumor cells in new ways, and a number of lines of evidence obtained by various investigators have provided important new views of the surface of mammalian cells. Recent work has, for example, revealed the structure of the histocompatibility antigens, which appear to be ubiquitous on mammalian cells of different types. The dependency on these antigens of lymphocyte interactions with viruses suggests a new hypothesis: histocompatibility molecules may serve as cell surface adaptors for the recognition of foreign antigens such as viruses by T cell receptors. Contrary to older notions, the molecules that make up the cell surface, including the histocompatibility antigens, are not fixed but move freely in the cell membrane, which is a bilayer of lipid. It has been shown in several laboratories that cross-linking of cell surface proteins or "receptors" such as antibodies leads to clustering of these mobile receptor molecules into patches which are subsequently collected as a cap at one pole of the cell. The interactions among different cells and signaling from the surface of each cell to the interior depend upon the structure and physico-chemical interactions of such receptors and on their linkage to structures underlying the cell membrane. Work in our laboratory has produced consistent evidence that the motion and distribution of cell surface molecules are under control of an intracellular system consisting of a network of special proteins. We have found, for example, that mitogenic lectins such as concanavalin A bind to the carbohydrate portions of surface receptors and cross-link them. This binding to some receptors leads to inhibition of motion of all other receptors on the cell surface, suggesting that the original cross-linkage affects a general network responsible for anchoring cell surface receptors. Explorations of the nature of this network suggest that it consists in part of assemblies below the surface membrane containing microfilaments and microtubules.