Maturation of dendritic cells (DC) is critical for efficient antigen presentation and initiation of an immune response. Interferon-γ (IFN-γ) is an important Th1 cytokine. In this study, we investigated the role of IFN-γ in DC maturation using either IFN-γ receptor deficient- or IFN-γ overexpression-models. We showed that immature DC generated in vitro from bone marrow (BM) progenitor cells produced low level of IFN-γ. After LPS stimulation, DC produced more IFN-γ, and IFN-γ productions were at comparable levels among C57BL/6 mice-derived DC (C57BL/6 DC), wild-type 129 mice-derived DC (129 DC) and IFN-γ receptor deficient 129 mice-derived DC (IFN-γR - / - DC). We found that IFN-γR - / - DC exhibited decreased expression of CD54, CD86, reduced capacity to secrete IL-1β and IL-12p70, and impaired capacity to stimulate alloreactive T cells and to drive Th1 differentiation. Transfection of IFN-γ gene into DC promoted DC to express higher CD40, CD54, CD80, CD86, CCR7 and I-A b , secrete more IL-1β and IL-12p70, and more potently activate both CD4 and CD8 T cells. These data suggest that IFN-γ signaling pathway is important for the maturation of DC in an autocrine fashion.