The aim of this study was to assess the usefulness of nitric oxide (NO) output measurement at multiple expiratory flow rates during diseases characterized by increased exhaled NO (FE(NO)) that could come from alveolar (liver cirrhosis) or bronchial (asthma) sources. It has been proposed that NO output measurements expressed as a function of expiratory flow allow alveolar NO concentration (FA(NO)) and maximal bronchial NO output (Qbr,max (NO)) to be computed. In 36 healthy nonsmoking subjects, we found that maximal bronchial NO output (37 +/- 3 nl/min) was correlated with the height of the subjects (p = 0.02). Alveolar NO concentration was 5.1 +/- 0.3 (SEM) ppb, which represented 31 +/- 2% and 61 +/- 3% of FE(NO) at 50 and 200 ml/s expiratory flow rate, respectively. Nonsmoking subjects with asthma (n = 28) were characterized by an increase in Qbr,max (NO) (133 +/- 14 nl/min) as compared with healthy nonsmoking subjects (p < 0.0001). FE(NO)50, FE(NO)200, and Qbr,max (NO) were equally efficient in differentiating subjects with asthma from healthy subjects. Patients with liver cirrhosis (n = 26, 14 smokers and 12 nonsmokers) had an increased FA(NO) compared with healthy subjects (cirrhosis: 8.3 +/- 0.9 ppb, healthy nonsmokers [n = 36] and smokers [n = 20], n = 56: 4.7 +/- 0.3 ppb, p < 0.05), which was correlated with the alveolar-arterial oxygen difference (p = 0.007). FA(NO) and FE(NO)200, but not FE(NO)50 values, allowed patients with liver cirrhosis to be differentiated from healthy subjects. These results suggest that a two-compartment model for NO output allows the increase in FE(NO) from alveolar sources to be differentiated from the increase from bronchial sources.