Antibody-producing hybridomas of myeloma SP2/O and spleen cells of BALB/c mouse immunized with pertussis toxoid and pertussis toxin were selected by the binding ability of the monoclonal antibody to the subunit protein of the toxin. Two monoclonal antibodies, 1B7 and 3F10, specific for a subunit which has no binding activity to haptoglobin and sheep erythrocytes, named S1, and one antibody, 1H2, for a subunit related to the binding activity of the pertussis toxin molecule to haptoglobin or sheep erythrocytes, named S4, were examined for mouse protective activity against pertussis infection. Antibody 1B7 not only neutralized leukocytosis-promoting and islet-activating activities of the toxin but also protected mice against intracerebral and aerosol challenge with Bordetella pertussis. The antibody, furthermore, showed therapeutic effects on mice showing severe clinical signs with pertussis infection. The other two antibodies, 3F10 and 1H2, showed neither neutralizing nor protecting activity, nor significant synergistic effects on antibody 1B7.