The role of elastase and alkaline protease in the pathogenesis of fatal infections caused by Pseudomonas aeruginosa was determined in mice treated with calcium chloride. Mortality increased significantly when solutions containing elastase were injected together with non-lethal inocula of strain PA 103, which does not produce proteolytic enzyme. In contrast, solutions containing alkaline protease did not increase mortality. In mice injected intramuscularly with strain PA 103 and calcium chloride, the organisms grew rapidly in the injected muscle but not in the liver. However, when elastase was injected together with strain PA 103 and calcium chloride, viable bacteria were also found in the liver. Moreover, the survival rate of mice challenged with elastase-producing strain 5 and calcium chloride was enhanced, and colonization of the liver prevented, by immunization with elastase toxoid. These results suggest that elastase contributes to the invasiveness of the organism.