Antigen recognition by T cells is determined by the antigen-specific T cell receptor (TcR), expressed on the surface of the T cell. This chapter focuses on T cell surface molecules involved in T cell adhesion, activation, and migration. These molecules function as receptors and a number of their ligands have been identified. CD4 and CD8 are nonpolymorphic cell surface glycoproteins expressed on subsets of thymocytes and mature peripheral T cells. Both CD4 and CD8 have been cloned and the predicted protein sequence demonstrates significant homology to immunoglobulin. The CD4 molecule exists as a monomer of 435 amino acids. It is a transmembrane protein with a cytoplasmic domain of 38 amino acids. The observation that the surface expression of CD4 and CD8 correlated not with the function but with the major histocompability complex (MHC) recognition or restriction by the T cell led to the proposal that CD4 and CD8 interacted with nonpolymorphic determinants of MHC class II and class I molecules, respectively. Adhesion alone is not the only function demonstrated for CD4 and CD8. CD4 appears to exert its greatest effect in T cell activation when recognizing MHC class II molecules in concert with recognition by the TcR of MHC class II molecules. Likewise, CD8 is most effective when interacting with MHC class I molecules in association with a TcR interacting with MHC class I molecules.