ABSTRACTWe evaluated the role of IL‐1 during Pseudomonas aeruginosa bacteremia by intravenously injecting P. aeruginosa strain D4 into IL‐1‐deficient and WT mice. The two strains showed equivalent mortality rates. However, when the mice were pretreated with cyclophosphamide, bacteremia‐induced mortality was significantly greater in the IL‐1‐deficient mice than in the WT mice (P < 0.01). We then investigated the role of neutrophils and macrophages in protecting IL‐1‐deficient mice from bacteremia by administering anti‐Gr‐1 antibody or liposomes containing dichloromethylene diphosphonate, respectively. After P. aeruginosa inoculation survival was significantly lower in the macrophage‐depleted IL‐1‐deficient mice than in the WT mice. In contrast, neutrophil depletion did not have this effect. Compared to the macrophage‐depleted WT mice, the macrophage‐depleted IL‐1‐deficient bacteremic mice had higher bacterial counts in various organs 48 and 72 hr post‐infection. They also had lower TNF‐α, IL‐6, and INF‐γ concentrations in their livers during the early phase of sepsis. Thus, IL‐1 deficiency becomes disadvantageous during P. aeruginosa bacteremia when it is accompanied by immunosuppression, particularly when macrophage functions are seriously impaired.