Assessing airway disease in young children with wheeze and/or cough is challenging. We conducted a prospective, descriptive study of lung function in children <3 years old with recurrent wheeze and/or cough, who had failed empiric antiasthma and/or antireflux therapy and subsequently underwent flexible bronchoscopy. Our goals were to describe radiographic, anatomical, microbiological, and physiological findings in these children, and generate hypotheses about their respiratory physiology. Plethysmography and raised-volume rapid thoracoabdominal compression (RVRTC) techniques were performed prior to bronchoscopy. Mean Z-scores (n = 19) were -1.34 for forced expiratory volume at 0.5 sec (FEV0.5), -2.28 for forced expiratory flows at 75% of forced vital capacity (FVC) (FEF75), -2.25 for forced expiratory flows between 25-75% of FVC (FEF25-75), 2.53 for functional residual capacity (FRC), and 2.23 for residual volume divided by total lung capacity (RV/TLC). Younger, shorter children had markedly depressed FEF75 and FEF25-75 Z-scores (P = 0.002 and P = <0.001, respectively). As expected, lower airway anatomical abnormalities, infection, and inflammation were common. Elevated FRC was associated with anatomical lower airway abnormalities (P = 0.03). FVC was higher in subjects with neutrophilic inflammation (P = 0.03). There was no association between other physiologic variables and bronchoscopic/bronchoalveolar lavage fluid findings. Half of those with elevated RV/TLC ratios (Z-score >2) had no evidence of chest radiograph hyperinflation. We conclude that in this population, plethysmography and RVRTC techniques are useful in identifying severity of hyperinflation and airflow obstruction, and we hypothesize that younger children may have relatively small airways caliber, significantly limiting airflow, and thus impairing secretion clearance and predisposing to lower airway infection. © 2006 Wiley-Liss, Inc.