Systemic colistin has shown efficacy against multidrug-resistant Pseudomonas aeruginosa and Acinetobacter spp., but it has presented poor results in pneumonia. Aerosolized polymyxin in cystic fibrosis patients has had good results. In this study, inhaled polymyxin B was used to treat respiratory infections by multidrug-resistant Gram-negative bacilli (MR-GNBs). Nineteen patients were treated with inhaled polymyxin B: 14 pneumonia, most of which had previously failed treatment with intravenous polymyxin B, and 5 tracheobronchitis. Inhaled polymyxin B was given at the dose of 500,000 IU twice a day after an aerosolized beta(2)-agonist. In pneumonia, inhaled and intravenous polymyxin B was given together. Median age was 69 years; 89% were in the intensive care unit. Sixteen infections (84%) were caused by P. aeruginosa. Klebsiella pneumoniae, Alcaligenes xylosoxidans, and Burkholderia sp. caused one infection each. In the 14 pneumonia cases, median of previous use of intravenous polymyxin B was 20 days (range, 0-32). Inhaled polymyxin B was used for a mean of 14 days (range, 4-25). Cure occurred in 10 (53%) patients, improvement in 8 (42%), and failure in 1. Nine patients died during hospitalization (all with pneumonia). Adverse events occurred in 4 patients without interruption of inhalation. This is the largest report using inhaled polymyxin B to treat nosocomial pneumonia by MR-GNB that had failed intravenous polymyxin B. It was also effective alone in P. aeruginosa tracheobronchitis.