Pseudomonas aeruginosa was inoculated into the lungs of normal and oxygen-exposed hamsters. Air-breathing animals developed focal bronchopneumonias but viable organisms were not recovered from the lungs after 3 days; bacteremia was not detected but P. aeruginosa was isolated from the livers of 3 of 12 animals with positive lung cultures. Pseudomonas aeruginosa infection shortened the survival time of oxygen-breathing hamsters, and organisms persisted in the lungs during oxygen exposure. Focal bronchopneumonias were uncommon in animals inoculated after 4 days of oxygen exposure; the predominant histopathologic finding was accentuation of diffuse alveolar damage and increased numbers of scattered neutrophils. Pseudomonas aeruginosa was recovered from the livers of 15 of 18 oxygen-exposed animals in which lung colony counts exceeded 103/lung; only 8 of these animals had demonstrable bacteremia. The concentration of elongation factor-2 in the livers and lungs of oxygen-exposed animals was reduced as colony counts of P. aeruginosa increased in the lungs of infected animals, suggesting exotoxin A activity in these organisms. These findings suggest that bacterial superinfection of injured lungs may account for both worsening lung function and impaired function of other organs.