Mouse hybridoma antibodies (IgG and IgM) to O side chain determinants of Escherichia coli strain Bort (O18ac:K1:H7) were evaluated for their in vitro and in vivo activities against E. coli strains. Both IgG and IgM were opsonic in vitro and protected newborn rats challenged with a K1 E. coli strain, but their activities were strain specific. The antibodies protected against a K1 strain possessing a homologous O serotype but not against one possessing a heterologous O serotype. These antibodies were not effective against the K5-encapsulated O18 E. coli strain (possessing a homologous O type) but protected against its unencapsulated derivative. The opsonic and protective activities of these antibodies were significantly greater with IgG than IgM. Both IgG and IgM, however, required complement for their activities. When IgM to lipopolysaccharide was given to newborn rats in conjunction with IgM monoclonal antibody to the group B meningococcal polysaccharide, the protective effect was significantly greater than that of either antibody alone. Combinations of two (or more) antibodies to different cell wall components may be more beneficial in preventing and treating E. coli infection.