We prepared an anti-idiotype (Id) abtibody against leptospirosis. Serum from rabbit immunized with mohoclonal antibody (MAb) LW2, which reacted to the main protective antigen prepared from Leptospira interrogans serovar lai, inhibited agglutination of the organism by MAb LW2. The immune rabbit serum was applied to a column coupled with normal mouse IgG as a ligand (first colume), and the unbound fraction eluted was applied to a column coupled with MAb LW2 as a ligand (second column). The bound fraction (anti-Id antibody) eluted from the second column inhibited the binding of MAb LW2 to sonicated leptospiral cells in ELISA. Mice produced antibodies against Leptospira by intraperitoneal immunization with the anti-Id antibody at doses of 2 μg/mouse or more. Hamsters were protected by immunization with the anti-Id antibody at doses of 2 and 20 μg/hamster from the lethal infection of Leptospira. This is the first report concerning the use of an anti-Id antibody against leptospirosis.