Denitrifying bacteria metabolize nitrogen oxides through assimilatory and dissimilatory pathways. These redox reactions may affect lung physiology. We hypothesized that airway colonization with denitrifying bacteria could alter nitrogen balance in the cystic fibrosis (CF) airway. We measured airway nitrogen redox species before and after antimicrobial therapy for Pseudomonas aeruginosa in patients with CF. We also studied ammonium (NH(4)(+)) and nitric oxide (NO) metabolism in clinical strains of P. aeruginosa in vitro and in CF sputum ex vivo. Ammonium concentrations in both sputum and tracheal aspirates decreased with therapy. Nitric oxide reductase (NOR) was present in clinical strains of P. aeruginosa, which both produced NH(4)(+) and consumed NO. Further, NO consumption by CF sputum was inhibited by tobramycin ex vivo. We conclude that treatment of pseudomonal lung infections is associated with decreased NH(4)(+) concentrations in the CF airways. In epithelial cells, NH(4)(+) inhibits chloride transport, and nitrogen oxides inhibit amiloride-sensitive sodium transport and augment chloride transport. We speculate that normalization of airway nitrogen redox balance could contribute to the beneficial effects of antipseudomonal therapy on lung function in CF.