We evaluated the effects of interleukin (IL)-10 on the maturation of human dendritic cells (DC) induced either by lipopolysaccharide (LPS) or CD40 engagement. For this purpose, DC generated by culturing plastic-adherent peripheral blood mononuclear cells for 7 days with granulocyte/macrophage-colony-stimulating factor and IL-4 were incubated for 3 days with either LPS (10 ng/ml) or 3T6 fibroblasts transfected with the gene encoding CD40 ligand, in absence or presence of IL-10. First we found that the membrane expression of CD83, a marker of mature DC, was inhibited by IL-10 when induced by LPS but not by CD40 engagement. Likewise, IL-10 inhibited LPS-induced but not CD40-dependent CD86 (B7.2) up-regulation on DC. Furthermore, IL-10 inhibited the production of IL-8 and tumor necrosis factor-alpha by DC when activated by LPS but not by CD40. In contrast, IL-10 inhibited IL-12 production in both activation systems. We conclude that IL-10 differentially influences LPS-dependent and CD40-dependent pathways of DC maturation.