This chapter discusses the biological inhibitors of lymphoid cell division. The biological inhibitors of lymphocyte responses can potentially affect several different processes, including the binding of antigen (recognition), the early steps of lymphocyte activation, or cell division itself. A factor can be considered to inhibit cell division directly only if it decreases either the division of unstimulated lymphocytes or the division of stimulated lymphocytes subsequent to the full period of activation and following the removal of the activator. If an inhibitor must be present during activation to exert its effect, but has no effect when added later, it inhibits either recognition or early activation, but not cell division directly. Specific interference with recognition is suggested if the factor inhibits the spontaneous rosette formation between human T cells and SRBC, and is strongly indicated if it competitively inhibits the binding of radiolabeled antigens or mitogens. Under ideal culture conditions, a commitment on the part of an activated lymphocyte to enter the replicative process involves its progression through the entire cycle of DNA synthesis (S), the second phase of growth (G 2 ), and mitosis (M). Inhibitors that interfere with the G 1 –S transition are of particular significance because they potentially interrupt the natural signals, which initiate cell division. By making use of the two phase markers, DNA synthesis and mitosis, one can determine whether a particular inhibitor is likely to exert its effect on the G 1 –S transition.