We studied the effect of IL-10 on the in vitro synthesis of IgE and IgG by human peripheral blood mononuclear cells (PBMC) following stimulation with anti-CD40 monoclonal antibody and IL-4. Anti-CD40- and IL-4-stimulated PBMC showed an increase in IL-10 synthesis together with increases in IgE and IgG production. Addition of anti-IL-10 antibody to this system suppressed IgE as well as IgG production without affecting the proliferation of PBMC. Addition of IL-10 enhanced IgE and IgG production if PBMC were activated with anti-CD40 and IL-4. PBMC costimulated with anti-CD40, IL-4 and IL-10 showed a remarkable increase in IL-6 production, but had no effect on IFN-gamma production. Addition of IL-10 to purified human tonsillar B cells stimulated with anti-CD40 and IL-4 enhanced B cell proliferation and IgG production, but not IgE production. These results suggest that IL-10 accelerates IgE production by anti-CD40- and IL-4-stimulated PBMC by enhancing IL-6 production through activation of T lymphocytes.