Abstract The opsonic capacities of IgGs purified from healthy blood donor sera with previously determined high cross-reactive antibody activities and IgGs with low cross-reactive antibody activities to Gram-negative lipopolysaccharide (LPS) core 1 were evaluated by chemiluminescence and bacterial phagocytosis against rough (R) and smooth (S) Gram-negative bacteria. IgGs with high cross-reactivity to LPS were shown to have a greater opsonic capacity for both rough and smooth bacteria than IgGs with low cross-reactivity. To confirm that the greater opsonic capacity was due to cross-reactive antibodies to LPS core and not due to O-serotype specific antibodies in the polyclonal IgGs, absorptions were performed with a cocktail of rough bacteria from both Salmonella minnesota and S. typhimurium followed by ELISA against S-LPS from different smooth Gram-negative bacteria. The results indicated that the major component of the reactivity to these S-LPS was due to cross-reactive antibodies specific for endotoxin core. To confirm that this was also the case for opsonic activity, absorptions with rough bacteria and homologous smooth bacteria were performed prior to reaction in the chemiluminescence assay with smooth bacteria. The results appear to confirm that cross-reactive antibodies to endotoxin core are responsible for a major component of the opsonic activity for smooth bacteria.