Pathogen-free rats were rendered neutropenic, given oral feedings of Pseudomonas aeruginosa 12.4.4, then monitored for fever. At the onset of fever, rats were given intravenous treatment with either anti-endotoxin monoclonal antibody (MAb) E5 or control MAb B55. Survival was significantly greater in E5- than in B55-treated animals (P < .01). Serum levels of both lipopolysaccharide and tumor necrosis factor-alpha were significantly reduced in E5- versus B55-treated rats 24 h after treatment (P < .01 and < .05, respectively). Rats were also treated with E5 or B55 in combination with a suboptimal dose of ciprofloxacin at fever onset and again 24 h later. Survival was significantly greater in ciprofloxacin-treated animals given E5 than in animals given B55 (P < .005). Posttreatment endotoxin levels were decreased in animals receiving E5 in combination with ciprofloxacin (P < .001) compared with B55-treated animals. These results indicate that therapy with anti-endotoxin MAb E5 alone or in combination with antimicrobial therapy improves survival in this bacteremic infection model of Pseudomonas sepsis.