Mouse hybridoma antibodies of several major classes against group B streptococcus type III have been produced. Mice were immunized with either whole heat-killed or acid-treated organisms to obtain antibodies against both the complete (sialated) or incomplete (nonsialated) forms of the type III polysaccharide. Resulting monoclonal antibodies showed exclusive specificity for either the complete or incomplete antigen. The ability of these antibodies to protect mice from a lethal challenge of live type III organisms was tested with a mucin model that permitted use of very small inocula given intraperitoneally with antibody and mucin. Antibodies specific for the nonsialated antigen were not protective, whether of IgM, IgG2a, or IgG3 isotypes. Antibodies specific for the complete antigen were, however, highly protective, including monoclonals of IgM, IgG2a, and IgA isotypes. These mouse monoclonal antibodies against group B streptococci that are directed against either complete or incomplete antigenic determinants, and include isotypes other than IgM, should be particularly useful for studying the mechanism of protection against experimental infection.