The E-rosette receptor (CD2, T11) is a differentiation antigen expressed on immature and mature human T lymphocytes. Activation of T cells from human peripheral blood with phytohemagglutinin (FHA) or with monoclonal antibody to the 0 3 -T i complex (anti-Leu-4) caused the expression of 0 2 to increase 10-to 20-fold. Dual parameter correlated analyses with antibody to the T cell growth factor ('I'CGF) receptor (anti-Tac) and anti-CD2 antibody demonstrated that the increase in CD2 expression occurred at the same time and on the same cells that expressed the TCGF receptor after stimulation with PHA. The increased expression of CD2 and the initial expression of Tac were totally inhibited by cycloheximide, but were not affected by sufficient actinomycin-D to block the T cell proliferative response. The expression of CD2 was compared with the expression of CD4 and CD8, i.e., T cell differentiation antigens on cytotoxic/suppressor or helper T cells, respectively. Although virtually all of the small percentage of freshly isolated Tac+ peripheral blood cells belonged to the CD4+, CD8-subset, both CD4+ and CD8+ T cells were equivalently activated by PHA to express Tac. By 20-30 hr after activation, the expression of CD4 or CD8 was initially decreased 10-50%. Subsequently, the expression of CD4 and CD8 returned to the levels on resting T cells but did not increase further. Therefore, the increase in CD2 expression does not reflect a universal property of cell surface antigens on activated T lymphocytes.Key terms: E-rosette receptor (CD2, T11); T cell growth factor or Interleukin-2 ('I'CGF, IL-2); Tar antigen; T cell differentiation antigens CD3-Ti, CD4, CD8; Monoclonal antibodies to Leu-Za, Leu-3a, Leu-4, Leu-5b, T11T cell precursors undergo differentiation and maturation in the thymus to be released as immunocompetent T cells that are found in lymph nodes and peripheral blood, These mature T cells express unique surface antigens that allow phenotypic identification of lymphocytes and lymphocyte subsets (3). The E-rosette receptor (CD2) (13,15,17,43) is a differentiation antigen that occurs on virtually all T cells, whereas CD4 and CD8 identify T cell subsets (31). In addition to these differentiation antigens, there are also activation antigens that are expressed only on stimulated cells. The receptor (Tac antigen) (45) for T cell growth factor (TCGF, also known as Interleukin-2, IL-2) is one such T cell activation antigen. The current data show that CD2 is an activation antigen as well, since its expression is increased by 10-to 20-fold on activated T cells.The initiation of a n immune response involves the stimulation of CD4+ and CD8+ T lymphocytes that ultimately express helper or cytotoxic/suppressor functions, respectively. TCGF is a polypeptide growth hormone initially produced early in T cell activation (38,44). It is essential for the proliferation of T cells stimulated with specific antigens or with polyclonal activators, e.g., antibody to the CD3-Ti complex (18,42) or lectins such as concanavalin-A (Con-A) or ph...