Rationale: The development of early lung disease in patients with cystic fibrosis (CF) remains poorly defined. Objective: Determine whether asymptomatic infants with CF have evidence for changes in airway structure when assessed by highresolution computed tomography, and whether airway structure correlates with airway function in this age group. Methods: Thirteen infants with CF (8-33 mo) and 13 control infants (7-25 mo) were evaluated. Airway wall and lumen areas were measured from three 1-mm-thick cross-sectional images obtained from upper, middle, and lower lobes during a respiratory pause with the lungs inflated to an airway pressure of 20 cm H 2 O. Lung tissue density was measured from images obtained during a respiratory pause at FRC. Forced expiratory flows were measured by the rapid thoracic compression technique in 11 infants with CF. Results: Airway wall area increased more per unit increase in airway size, whereas airway lumen area increased less per unit increase in airway size in the CF than in the control group. Among infants with CF, a greater ratio of wall to lumen area correlated with lower airway function. In addition, lung density at relaxed (passive) FRC was lower for infants with CF than for control infants (0.38 vs. 0.43 g/ml; p Ͻ 0.02). Conclusions: Our results indicate that infants with CF have thickened airway walls, narrowed airway lumens, and air trapping, when assessed by high-resolution computed tomography, and measurements of airway structure correlated with airway function. Keywords: airway structure; high-resolution computed tomography; lung disease Our understanding of the early pulmonary pathophysiology of cystic fibrosis (CF) has greatly expanded over the last two decades. Measurements of lung function have demonstrated the presence of airway obstruction in infants with CF without respiratory symptoms (1-4), and bronchoalveolar lavage has demonstrated that airway inflammation can be present even among infants with CF without respiratory symptoms (5, 6). Despite these advancements, our current knowledge about structural changes in the lungs of infants with CF is very limited and has primarily been obtained from autopsy studies. Lungs of newborns with CF have essentially normal histology; however, autopsied lungs from severely affected infants with CF can dem- onstrate bronchiectasis as early as age 6 mo (7, 8). The availability of autopsied lungs of infants is currently very limited, and those obtained are most likely atypical of the general CF population. In adults and cooperative older children, high-resolution computed tomography (HRCT) has emerged as a powerful technique to assess lung structure in vivo (9, 10). Evaluations of adults with asthma, chronic obstructive pulmonary disease, or emphysema have demonstrated changes in lung structure on CT images, and quantitative measures of airway size, wall thickness, and parenchymal tissue density, as well as measures of pulmonary function have been consistent with histologic findings (11-15). Studies using CT imaging of older chi...