After intradermal infection of mice with the obligatory intracellular parasite Leishmania major, Langerhans cells (LC) are intimately involved in the induction of the primary T-cell immune response. LC can phagocytose Leishmania and transport ingested parasites from the infected skin to the regional lymph nodes. Since TNF alpha and IL-1 beta have been shown to induce LC migration after epicutaneous exposure to skin-sensitizing chemicals, we investigated the involvement of both cytokines in the migration of Leishmania-infected LC. In addition, the relevance of two chemokines of the beta subfamily, macrophage inflammatory protein 1 alpha (MIP-1 alpha) and macrophage chemoattractant protein 1 (MCP-1), was analyzed. In vivo depletion of TNF alpha significantly reduced the amount of infected LC and the parasite load in the draining lymph nodes. Administration of recombinant TNF alpha caused the reverse effect. In contrast, the depletion of IL-1 beta enhanced the parasite-induced LC migration, whereas treatment with recombinant IL-1 beta, as well as recombinant MIP-1 alpha, reduced the rate of infected LC in the lymph nodes. MCP-1 did not influence LC migration. Our data demonstrate that TNF alpha and IL-1 beta are regulating the LC-mediated transport of Leishmania and also provide evidence for the involvement of macrophage attractant chemokines in this process.