DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin) binds human immunodeficiency virus type 1 (HIV-1) and facilitates transfer of virus to permissive cells. Leishmania parasites also exploit DC-SIGN as a receptor. Here, we report that transfer of HIV-1 to target cells is markedly reduced when DC-SIGN(+) cells are preincubated with Leishmania amastigotes before pulsing with virions. Moreover, binding of HIV-1 to DC-SIGN(+) cells is diminished by the presence of Leishmania amastigotes. Our findings provide novel insight into the complex interactions between HIV-1 and Leishmania parasites. The ability of both HIV-1 and Leishmania parasites to bind to the same cell-surface constituent to gain entry into dendritic cells might have an impact on the immunological and pathological events associated with HIV-1 infection.