BACKGROUND: Nitric oxide (NO) gas concentrations are high in the expired air of individuals with asthma, but not consistently so in the expired air of people with pneumonia. S-nitrosothiols are naturally occurring bronchodilators, the concentrations of which are raised in the airways of patients with pneumonia. Airway S-nitrosothiols have not been studied in asthma. METHODS: Tracheal S-nitrosothiol concentrations from eight asthmatic children in respiratory failure were compared with those of 21 children undergoing elective surgery. RESULTS: Mean S-nitrosothiol concentrations in asthmatic children were lower than in normal children (65 [SD 45] nmol/L vs 502 [SD 429] nmol/L) and did not vary with inspired oxygen concentration or airway thiol concentration. INTERPRETATION: Severe asthma is associated with low concentrations of airway S-nitrosothiols. This is the first reported deficiency of an endogenous bronchodilator in the human asthmatic airway lining fluid. We suggest that S-nitrosothiol metabolism may be a target for the development of new asthma therapies.