Exhaled nitric oxide (NO) remains a promising noninvasive index for monitoring inflammatory lung diseases; however, the plateau concentration (C(NO,plat)) is nonspecific and requires a constant exhalation flow rate. We utilized a new technique that employs a variable flow rate to estimate key flow-independent parameters characteristic of NO exchange in a group (n = 9) of 10 to 14 yr-old healthy children and children with cystic fibrosis (CF): maximum flux of NO from the airways (J(NO,max'), pl s(-1)), diffusing capacity of NO in the airways (D(NO,air'), pl s(-1) ppb(-1)), steady-state alveolar concentration (C(alv,ss'), ppb), and mean tissue concentration of NO in the airways (C(tiss,air'), ppb). We determined the following mean (+/- SD) values in the healthy children and patients with CF for J(NO,max'), D(NO,air'), C(alv,ss'), and C(tiss,air'), respectively: 784 +/- 465 and 607 +/- 648 pl s(-1); 4.82 +/- 3.07 and 17.6 +/- 12.1 pl s(-1) ppb(-1); 4.63 +/- 3.59 and 1.96 +/- 1.18 ppb; and 198 +/- 131 and 38 +/- 25 ppb. D(NO,air) is elevated (p = 0.007), and both C(alv,ss) and C(tiss,air) are reduced (p = 0.05 and 0.002, respectively) in CF. In contrast, C(NO,plat) for healthy control subjects and patients with CF are not statistically different at both exhalation flow rates of 50 ml/s (17.5 +/- 11.5 and 11.5 +/- 8.97) and at 250 ml/s (7.11 +/- 5.36 and 4.28 +/- 3.43). We conclude that D(NO,air'), C(tiss,air'), and C(alv,ss) may be useful noninvasive markers of CF.