To determine the effects of continuous positive airway pressure (CPAP) on ventilatory response to CO2 and inspiratory and expiratory duration in preterm infants, 24 preterm infants with an average birth weight of 1220 g were studied at a mean age of 10.6 days. CPAP was applied via an uncuffed endotracheal tube. Testings were performed between ambient pressure and a positive airway pressure of 10 cm H2O. Approximately 2/3 of the applied pressure was transmitted to the esophagus. All infants demonstrated a ventilatory response to carbon dioxide of less than 50 ml/min per mm Hg Pco2 at ambient pressure, and no infant showed significant improvement at increasing levels of CPAP. Drive to breathe, as reflected in the inspiratory flow rate (Vt/Ti) also failed to change significantly. It may be concluded that in the apparent absence of significant changes in lung volume, CPAP fails to increase sensitivity to CO2 in preterm infants recovering from hyaline membrane disease.