Efforts to define host defense mechanisms against Leishmania are aimed at developing strategies for prevention (vaccines) and treatment (chemotherapeutic or immunotherapeutic) of leishmaniasis. Ongoing or proposed studies include (1) characterization of host-parasite interaction at the plasma membrane level, (2) examination of macrophage activation of leishmanicidal mechanisms in vitro, and (3) cell-mediated cytotoxic pathways against host cells or free parasites. Host cell-parasite interactions are studied by treating parasites or mononuclear phagocytes with proteases and examining the effects of this treatment on attachment to monocytes/macrophages by the parasite, and parasite entry into host cells. Metabolic inhibitors added to cultures of cytochalasin treated host cells will permit definition of energy requirements of the parasite for the attachment phase. Infected macrophages (mouse) or human monocytes are treated in vitro with lymphokines or other macrophages (mouse) or human monocytes are treated in vitro with lymphokines or other macrophage activating agents and induction of parasite killing is examined. Methodologies to assess whether "killer" lymphocytes or antibody-dependent cell-mediated cytotoxic mechanisms can kill infected host cells or free parasites in vitro are to be developed. Although these studies are presently being performed in the U.S., they serve as a foundation for planned field studies of patients with leishmaniasis in Brazil.