We have analysed the role of IL-6 in activation of human lymphocytes isolated from peripheral blood. We found little effect of IL-6 on proliferation of T cells. IL-6 did stimulate production of IgM by B cells. However, it did not behave as a terminal differentiation factor and was required only during the first two days of the culture. Under most conventional stimulation conditions T cells themselves produce little or no IL-6. High IL-6 production could be induced by stimulating the cells with a combination of phorbol-12-myristate 13-acetate (PMA) and anti-CD28 antibodies.