Background: Exhaled breath condensate(EBC) pH is 2 log orders below normal during acute asthma exacerbations and returns to normal with antiinflammatory therapy. However, the determinants of EBC pH, particularly in stable asthma, are poorly understood. We hypothesized that patients with severe asthma would have low EBC pH and that there would be an asthma subpopulation of patients with characteristically low values. Methods: We studied the association of EBC pH with clinical characteristics in 572 stable subjects enrolled in the Severe Asthma Research Program. These included 250 subjects with severe asthma, 291 with nonsevere asthma, and 31 healthy control subjects. Results: Overall, EBC in this population of stable, treated study subjects was not lower in severe asthma (8.02;interquartile range [IQR], 7.61-8.41) or nonsevere asthma (7.90;IQR, 7.52-8.20) than in control subjects (7.9;IQR, 7.40-8.20). However, in subjects with asthma the data clustered below and above pH 6.5. Subjects in the subpopulation with pH < 6.5 had lower fraction of exhaled NO (FENO) values (FENO = 22.6 ± 18.1 parts per billion) than those with pH ≥ 6.5 (39.9 ± 40.2 parts per billion; P<.0001). By multiple linear regression, low EBC pH was associated with high BMI, high BAL neutrophil counts, low prebronchodilator FEV1 ratio, high allergy symptoms, race other than white, and gastroesophageal reflux symptoms. Conclusion: Asthma is a complex syndrome. Subjects who are not experiencing an exacerbation but have low EBC pH appear to be a unique subpopulation.