Multiple-breath N2 washouts were performed before and after bronchodilation in 15 patients with moderately severe asthma (mean age 13 years), and in 11 patients with cystic fibrosis (CF; mean age 16 years) matched for FEV1. Eighteen healthy subjects (mean age 15 years) were studied before bronchodilation. The lung clearance index (LCI) was determined from the washout curve and gas trapping was assessed from five subsequent large breaths. Analysis of the progression of the concentration normalized phase III slopes (SnIII) over the washout was used to determine inhomogeneity in the conducting airways (Scond) and inhomogeneity close to or within the gas exchange zone (Sacin). Before bronchodilation all washout indexes were abnormal in the CF group, and all but Sacin in the asthma group. Two indexes were higher in CF than in asthma: LCI (11.5 (3.3) vs. 8.7 (1.3); P < 0.01), and Sacin (0.307 (0.207) vs. 0.142 (0.071); P < 0.01), while gas trapping indexes and Scond (0.151 (0.071) vs. 0.127 (0.041)) did not differ significantly. After bronchodilation, all indexes improved in asthma and only Scond remained abnormally elevated. In CF, only a modest but statistically significant Sacin improvement was seen and all indexes stayed abnormal. The study shows that overall ventilation inhomogeneity and particularly inhomogeneity in or close to the gas exchange zone are more pronounced in CF than in asthma matched for FEV1, while inhomogeneity in the conducting airway zone is similar. After bronchodilation, residual abnormalities of airway function are seen all through the airway tree in CF but only in the conducting airways in asthma. Pediatr Pulmonol. 2007; 42:168-176. © 2006 Wiley-Liss, Inc.