Pneumonia is associated with elevated concentrations of the proinflammatory cytokine interleukin (IL)-1 in the pulmonary compartment. To study the role of IL-1 in the pathogenesis of Pseudomonas pneumonia, IL-1 receptor type 1 gene-deficient (IL-1R −/−) mice and wild-type mice were intranasally inoculated with Pseudomonas aeruginosa. The absence of the IL-1 signal attenuated the outgrowth ofPseudomonas in lungs, as reflected by an increasing number of colony-forming units (cfu) during Pseudomonaspneumonia in wild-type mice and a concurrently decreasing number of cfu during pulmonary infection in IL-1R −/− mice (P < 0.05, IL-1R −/− mice vs. wild-type mice). Influx of neutrophils was decreased in bronchoalveolar lavage fluids in IL-1R −/− mice compared with wild-type mice. Similarly, lung levels of cytokines (tumor necrosis factor-α, IL-6) and chemokines (macrophage inflammatory protein-2 and KC) were lower inIL-1R −/− mice 24 h postinoculation. Consistent with results obtained in IL-1R −/− mice, treatment of wild-type mice with IL-1R antagonist also diminished outgrowth ofPseudomonas when compared with wild-type mice treated with vehicle (P < 0.05). These results demonstrate that an absence or reduction in endogenous IL-1 activity improves host defense against Pseudomonas pneumonia while suppressing the inflammatory response.