The role of interleukin 2 (IL2) in the induction of human B cell differentiation in vitro was studied. IL2 was unable to induce immunoglobulin (Ig) production in non-T cells either in the presence or absence of pokeweed mitogen (PWM). However, IL2 alone could induce Ig production in non-T cells when irradiated T cells were present. Similar to the PWM-driven system helper activity was delivered by T4+ but not T8+ cells. Apparently, IL2 acts on T4+ cells and induces these cells to deliver the actual helper signal(s) for Ig production by B cells. Whereas in the PWM-driven system only T8+ cells suppress Ig synthesis, IL2-driven Ig synthesis was suppressed by both T4+ and T8+ cells added to a mixture of non-T cells and irradiated T4+ cells. This suppressor activity could be abrogated by irradiation. PWM was shown to induce IL2 production in both T4+ and T8+ cells. Moreover, PWM-induced Ig synthesis, like IL2-induced Ig synthesis, could be totally abrogated by a monoclonal antibody against the human IL2 receptor (anti-Tac). These findings, coupled to the innate Ig-inducing capacity of IL2, indicate a role for IL2 in the PWM-driven system. The mechanism of suppression in both the PWM- and the IL2-driven systems was not shortage of IL2 in the culture due to consumption or inhibition of production of IL2. Moreover, the T8+ cells produced IL2, despite their failure to help Ig synthesis. Helper T cell activity can thus be divided into two distinct activities: IL2 production and the ability to deliver the actual helper signal such as helper factors for B cell differentiation. This insight allows a better evaluation of the immunoregulatory activities of T cell subsets in health and disease.