The capacity of pertussis toxin (PT) to induce maturation and functional activities of human monocyte–derived dendritic cells (DCs) was investigated. Both native PT (nPT) and genetically detoxified PT (dPT) efficiently promoted expression on DCs of CD80, CD86, human leukocyte antigen–DR, and CD83 markers, alloreactive antigen presentation, and cytokine production, primarily interferon (IFN)–γ. Although they did not affect interleukin (IL)–10 production by lipopolysaccharide (LPS)–stimulated DCs, both nPT and dPT strongly synergized with LPS for IL-12 production. PTs plus LPS-stimulated DCs secreted soluble factors fostering IFN-γ but not IL-4 and IL-5 production by naive T cells. T helper type 1 (Th1) polarization was, as alloreactive antigen presentation, inhibited by anti–IL-12 monoclonal antibody. These findings support the notion that nPT, in addition to inducing specific immune response, is a potent Th1 adjuvant and that dPT fully preserves this adjuvanticity. The synergic interaction between PT and LPS in IL-12 production might be relevant for the mechanisms of vaccine-induced protection