Leishmania donovani GP36 glycoprotein is the main antigen of the FML Fucose Mannose Ligand (FML) complex specifically recognized by sera of kala-azar human patients. The GP36 was isolated by chemical elution+sonication and used for Balb/c mouse vaccination in combination with saponin, by the s.c. route, inducing a strong and specific protective effect against experimental visceral leishmaniasis shown by the increase of: specific IgG antibodies (82.6%), mainly IgG2a, the delayed type of hypersensitivity to promastigote lysate (37.8%, P<0.001), the in vitro cellular proliferative response to GP36 of ganglia lymphocytes (53.5%, P<0.005) and the decrease of liver parasite burden (68.1%, P<0.025). Saponin treated controls reacted significantly differently from GP36 vaccinated animals at all the assayed variables (P<0.05). GP36 induced significant protection against murine visceral leishmaniasis at concentrations commonly used for vaccination with recombinant antigens.