The protective capacity of passively transferred immunoglobulin G (IgG) fractions from antitoxin (AT-IgG), antielastase (AE-IgG), and antilipopolysaccharide (ALPS-IgG) against Pseudomonas aeruginosa infection was evaluated in a murine burn wound sepsis model. Complete protection was afforded by homologous ALPS-IgG against intermediate challenge doses (10 50% lethal doses) of P. aeruginosa PA220, whereas AT-IgG and AE-IgG offered no significant protection (P less than 0.5). The simultaneous transfer of AT-IgG or AE-IgG with ALPS-IgG gave no additional protection above that seen with ALPS-IgG alone. The transfer of ALPS-IgG did not dramatically alter bacterial multiplication in the skin at the site of infection. However, bacteremia and infection of the liver were prevented. In parallel experiments, AT-IgG or AE-IgG did not significantly alter either the course of the infection or the number of bacteria seen in the blood, liver, or skin when compared with controls. ALPS-IgG administered 24 h before infection, at the time of infection, or 4 h postinfection provided complete protection. Even when ALPS-IgG was transferred at a time when the infection was well established locally in the skin (8 h postinfection), highly significant protection (P greater than 0.999) was obtained. Protection afforded by ALPS-IgG was serotype specific. These results indicate that antibody to lipopolysaccharide is of critical importance for protection against P. aeruginosa challenge in a relevant animal model.