In vitro and in vivo studies identify IL-10 as a key cytokine that inhibits cell-mediated immunity and inflammation while promoting humoral responses. The present review summarizes our studies regarding the ability of B cells to secrete IL-10. When established lines are considered, the production of human IL-10 is restricted to mature B-cell lines and correlates with Epstein-Barr Virus (EBV) expression. Accordingly, EBV infection induces purified tonsil B lym phocytes to produce high levels of human IL-10, whereas viral IL-10 (encoded by EBV) remains undetectable. Exogenous IL-10 enhances EBV-induced B-cell growth, while a neutralizing anti-IL-10 antibody inhibits it, suggesting that IL-10 acts as an autocrine growth factor for EBV-infected B lymphocytes. Normal B lymphocytes secrete lower levels of human IL-10 following activation through B-cell receptor or CD40 antigen. While addition of exogenous IL-4 diminishes CD40-induced secretion of IL-10, addition of Staphyloccocus aureus Cowan I (SAC) particles increases it. Neutralization of endogenous IL-10 does not alter growth of CD40-activated B cells but inhibits their IgG, IgA, and IgM secretion, especially when costimulated with SAC particles. Finally, the simul taneous blocking of both endogenous IL-10 and IL-6 inhibits two-thirds of the production of the three isotypes when B cells were triggered through CD40 in the presence of SAC particles, suggesting that IL-10 synergizes with IL-6 to sustain differentiation of CD40-activated B lymphocytes. Overexpression of B-cell-derived IL-10 is likely to contribute in vivo to different pathologies such as B-lymphoproliferative disorders and autoimmune diseases.