• Idiopathic apnea in preterm infants, more than 30 weeks of gestation, after the first week of life is uncommon and poorly understood. To study ventilatory control in these infants we measured minute ventilation, respiratory frequency, tidal volume, end-tidal oxygen pressure and carbon dioxide pressure, and transcutaneous oxygen pressure before and during the fifth minute of breathing 4% carbon dioxide in air. Nine healthy preterm infants and eight infants with three or more episodes of apnea (≥20 s) in 24 hours were studied during active sleep. We found that infants with apnea had a significantly increased alveolar carbon dioxide pressure while respiratory frequency, minute ventilation, and slope were significantly decreased. Alveolar-transcutaneous oxygen gradients were essentially unchanged. These preterm infants with apnea have a decreased carbon dioxide sensitivity. They have a decreased minute ventilation primarily as a result of decreased respiratory frequency and their alveolar-transcutaneous oxygen gradient is normal. Our findings suggest that the major deficit in these infants is a central disturbance in the regulation of breathing.