Monoclonal antibody technology has permitted researchers to dissect out the protective antibody response to conserved regions of gram-negative bacillary lipopolysaccharides (endotoxins). Some anticore antibodies can bind to lipid A and have a neutralizing, but not opsonic, activity; these antibodies are usually IgM. IgG antibodies to outer core regions may be weakly opsonic. The outcome of animal protection studies is critically dependent on the choice of challenge organism, dose, timing and rate of antibody administration, and additional factors such as antimicrobial therapy. Protective activity against a wide variety of gram-negative bacillary challenges with the IgM anticore and lipid A reactive antibody, which we have designated E5, is reviewed. Protection in a therapeutic model is demonstrable when the antibody is used in conjunction with appropriate antimicrobial therapy. This antibody is now being assessed in clinical trials. Optimal use of monoclonal antibodies may involve a "cocktail" of antibodies with complementary binding specificities.