Human interleukin-12 (IL-12) is a 70-kDa polypeptide that activates human natural killer cells. It has been purified from the culture supernatant of a human Epstein-Barr virus-transformed B cell line and cloned. We show that native as well as recombinant IL-12 promoted growth of Staphylococcus aureus Cowan I strain (SAC) or anti-mu antibody-activated B cells in a dose-dependent manner. IL-12 also acted in synergy with IL-2 in growth and differentiation of SAC-activated B cells. Since anti-interferon (IFN)-gamma antibody completely abrogates B-cell growth factor (BCGF) activity of IL-12, the BCGF activity is mediated by IFN-gamma. This conclusion is clearly supported by the results that IL-12 indeed induced IFN-gamma production by activated B cells. These results suggest that the B cell proliferative effect of IL-12 may be mediated by autocrine IFN-gamma.