Pulmonary function during the early development of bronchopulmonary dysplasia (BPD) in premature infants is not well understood. Furthermore, it is not known how early airway reactivity appears in BPD. During a 14-month period we studied 32 infants (mean gestational age, 27.3 wk; mean birth weight, 1.02 kg) with respiratory distress syndrome in whom BPD eventually developed. We obtained maximal expiratory flow-volume (MEFV) curves by manual inflation of the lung followed by forced deflation with a negative pressure on 64 occasions (mean postnatal age, 43.1 days). At each test MEFV curves were obtained in 3 conditions: baseline; after normal saline aerosolization with manual ventilation as a control; and after bronchodilator. Maximal expiratory flow at 25% of FVC (Vmax25) was markedly decreased at baseline and remained decreased after saline control. The FVC also was decreased in both baseline and saline control studies. After bronchodilator there was a marked (p less than 0.001) increase in Vmax25 (+214% above saline control) together with a significant (p less than 0.001) increase in FVC (+21%). Of 23 infants studied after 3 wk of postnatal age, 21 exhibited a more than 30% increase in Vmax25 above control (defined as airway reactivity). The remaining 2 infants were already receiving bronchodilator therapy. The most premature infant with demonstrable airway reactivity was 26 wk postconception, and the youngest was 12 days old. In 13 infants who were studied initially before 3 wk of age, there was a highly significant correlation (r = 0.91 p less than 0.001) between the degree of airway reactivity and the severity of respiratory disease as determined by the duration of ventilator dependence. Airway reactivity may play an important role in the development and severity of BPD.