Pulmonary resistance is elevated early in preterm infants who later develop chronic lung disease. This early increase in pulmonary resistance may play a role in the development of severe bronchopulmonary dysplasia (BPD). A beta-2-agonist (isoetharine HCl) was used as an aerosol in 13 preterm infants with elevated pulmonary resistance. Their birthweight ranged from 880 to 1630 g, their gestational age from 27 to 34 weeks, and their post natal age from 3 to 18 days. All infants had required mechanical ventilation for respiratory distress syndrome and therefore were at risk to develop BPD. Pulmonary mechanics were measured before and 30 minutes after aerosol treatment, determining inspiratory and expiratory flow with a pneumotachometer and esophageal pressure through a water-filled feeding tube. The treatment was well tolerated with no significant changes in blood pressure, heart rate, or respiratory rate. Pulmonary resistance decreased significantly from 130 +/- 35 cm H2O/L/sec to 89 +/- 24 cm H2O/L/sec after the treatment. Dynamic lung compliance increased in 11 of the 13 infants. It is concluded that beta-2-agonist nebulization is effective in reducing the early increase in pulmonary resistance that occurs in preterm infants who are at risk of developing BPD. This effect may be due to relaxation of bronchial smooth muscle, to improved mucociliary transport, and to a reduction in peribronchial edema.