Abstract Recent investigations demonstrate that B lymphocytes possess an oxygen-generating system which is similar to the phagocytic NADPH-oxidase system. Reduction of nitroblue tetrazolium by stimulated tonsillar B cells is inhibited by superoxide dismutase (SOD). However, the biological significance of the superoxide-generating property of B cells remains to be explored. In this study, we examined the immunomodulatory effect of a recombinant human SOD (rh-SOD) on the activation of human B lymphocytes in vitro.A supplement of rh-SOD in the B cell culture increased the proliferation of unstimulated B cells in the presence of SAC, but not of SAC-preactivated B cells in the presence of cytokines such as IL-2 or IL-4. In addition, rh-SOD enhanced the immunoglobulin generation by B cells at the terminal stage of differentiation. Inactivation of the enzymatic activity of SOD by treatment with anti-SOD antibody abrogated the enhancing effects. These data suggest that the superoxide—generating system in B cells may be involved in the cellular activation process.