Experimental leishmaniasis represents a suitable model to analyze Th1-type associated immunity. In C57BL/6 mice healing of leishmaniasis correlates with activation of Th1 cells. Recently, it could be demonstrated that dermal dendritic cells rather than epidermal Langerhans cells are responsible for the activation of Th1 cells after infection, indicating a necessary reconsideration of the role of Langerhans cells. In our current work, epidermal application of Leishmania-antigen prior to infection resulted in an atypical course of disease that is characterized by an impaired Leishmania-specific Th1 response. Consequently, these mice cannot manage an efficient elimination of the parasites at the site of infection. These data point to the activation of immunomodulatory effects by epidermal incorporation of antigen.