We evaluated the immunoglobulin class responsible for the protective activity in serum obtained from humans and rabbits after immunization with the R595 (Re chemotype) mutant of Salmonella minnesota. Whole serum obtained before immunization and the IgG and IgM fractions failed to protect mice against lethal challenge with viable Klebsiella pneumoniae or Morganella morganii or with Salmonella typhi lipopolysaccharide (LPS). The protective activity of postimmunization serum resided solely in IgM antibody, whereas IgG antibody exhibited no protective activity. IgM antibody to the Re mutant was protective against bacterial challenge with both test strains of bacteria and S. typhi LPS. IgM antibody, at approximately the same concentration present in postimmunization serum, increased the LD50 of K. pneumoniae from less than 8.0 x 10(2) to greater than 2.0 x 10(4). These findings indicate that commercially prepared human IgG with high titers of antibody to antigens of the core portion of LPS would have little clinical utility.