The immunological hallmark of SLE is B cell hyperactivity. CD154 (CD40-L) is normally expressed in activated T cells, and plays an important role in T-B interactions. Its expression is increased in SLE T cells. Additionally, its expression on B cells leads to the development of SLE-like disease in a transgenic model. IL-10 is a key cytokine in the disturbed SLE immune system. The aim of this work was to explore the relation between IL-10 and CD154 expression in SLE B cells. We studied 11 SLE patients and 10 healthy volunteers. Mononuclear cells were isolated from peripheral blood and cultured in the presence or absence of Cowan I Strain Staphylococcus (CSS). Surface CD154 and intracytoplasmic IL-10 expression were quantified with flow cytometry. In basal conditions, CD154 expression was not different in patients and controls. B cell stimulation did not cause a significant increase in CD154 expression in control B cells. However, its expression increased 2 times in B cells obtained from SLE patients. IL-10 expression was confined to CD154(+) cells. Our results show that IL-10 production is intimately linked to CD154 expression in B cells, and that the IL-10(+)CD154(+) B cell subset increases abnormally when SLE-derived cells are stimulated with CSS.