Most B-cell differentiation systems are complicated by the fact that they are both T-cell- and monocyte-dependent. Immobilized anti-CD3 antibodies induce monocyte-independent T-cell activation, allowing investigation of the role of interleukin-6 (IL6) in the process of B-cell differentiation. We observed that in this system, the addition of monocytes to purified lymphocytes does not influence T-cell proliferation but it does enhance the induction of Ig production. IL6 can specifically replace monocytes in this enhancing effect on both IgM and IgG production. Anti-CD3-induced Ig production appears to be dependent on both IL2 and IL6 since it was inhibited by anti-CD25 (anti-IL2-R) antibodies as well as by anti-IL6 antibodies. Kinetic studies of IL6 addition showed that IL6 is only necessary during the first two days of culture. Our data indicate that IL6 plays an essential role in anti-CD3-induced Ig production, but not as a terminal differentiation factor.