The gp63 gene of Leishmania major was transformed into the AroA- vaccine strain of Salmonella typhimurium (SL3261). The construct (SL3261-gp63), which stably expresses the gp63 Ag in vitro, was used to immunize CBA mice by the oral route. Spleen cells from mice inoculated with SL3261-gp63 developed antibody and proliferative T cell response to L. major. They did not express detectable delayed-type hypersensitivity reactivity. The activated T cells are mainly CD4+ and secrete IL-2 and IFN-gamma but no IL-4. The orally immunized mice developed significant resistance against a challenge L. major infection. We have, therefore, demonstrated the feasibility of oral vaccination against leishmaniasis and that the oral route of antigen delivery via the heterologous carrier may preferentially induce Th1 subsets of CD4+ cells.