A PIVOTAL EVENT in the generation of immune responses to most antigens is the clonal activation of antigen-specific T lymphocytes. The abilities of T cells to recognize and respond to antigenic stimuli are mediated through the clonotypically expressed T-cell antigen receptor (TCR). Engagement of the TCR by antigens or other stimulatory ligands triggers a cascade of biochemical events which culminate in T-cell activation, growth and differentiation. Recent studies have outlined a unifying model for the process of signal transduction through the TCR. Although our current understanding of the relevant enzymatic machinery is far from complete, a compelling body of evidence indicates that an increase in protein tyrosine kinase (PTK) activity represents the initial transduction event induced by TCR crosslinkage. This review highlights recent insights into the biochemistry of TCR-mediated signaling, with particular focus on the role of protein tyrosine phosphorylation in coupling this receptor to downstream activation pathways in antigen-stimulated T cells. Before examining the TCR-linked signaling mechanism, it is important to recognize the remarkably diverse array of biological responses regulated by this receptor. During T-cell development, signals transduced through the TCR play determinant roles in the selection and maturation of T-cell progenitors in the thymus 1. Post-thymic T cells are activated by interactions with antigen-presenting cells that display antigenic peptides bound to'self'major histocompatibility complex (MHC)-encoded molecules. The term'activation'refers to a highly pleiotropic set of cellular responses that include cell cycle entry (GO to G1 phase transition) and the expression of high-affinity receptors for the T-cell growth factors, interleukin 2 (IL-2) and, in some T-cell subsets, interleukin 4 (IL-4). The activated cells thereby acquire'competence'to undergo cell cycle progression and mitosis in response to IL-2 or IL-4 stimulation.