Outer membrane (OM) protein F (porin) was purified by extraction from polyacrylamide gels of cell envelope proteins of the Pseudomonas aeruginosa PAO1 strain. Mice were immunized intramuscularly with 10 μg of protein F preparation on days 1 and 14 and then subjected to burn and challenge on day 28. Protein F immunization afforded significant protection above that provided by PAO1 lipopolysaccharide (LPS) immunization against subsequent challenge with six of six heterologous LPS immunotype strains of P. aeruginosa. By an ELISA, the murine immune response revealed an IgG titer of 5,120 to protein F by day 30. Immunoblot analysis of antisera from protein F-immunized mice revealed bands with both protein F and protein H of cell envelopes of all immunotypes tested. Active immunization with OM protein H did not, however, afford significant protection to mice in this burned mouse model. These data show the efficacy of OM protein F as a protective vaccine in a murine model representative of human infection.