Because neonatal apnea is frequently associated with airway obstruction, we compared relative changes in activity between various upper airway muscles and the diaphragm during hypercapnic stimulation. The technique of hyperoxic CO2rebreathing was employed in 17 healthy, sleeping preterm infants studied at a postnatal age of 32 ± 12 days. Surface diaphragm (DIA) electromyograms (EMGs) were recorded in all infants, and noninvasive measurements of posterior cricoarytenoid (PCA), genioglossus (GG), and alae nasi (AN) EMGs were analyzed in 11, 9, and 8 infants, respectively. During the control period, consistent phasic EMGs were recorded from the DIA in all infants and from the PCA in 8 infants, but from the GG and AN each in only one infant. During CO2rebreathing, minute ventilation and end-tidal CO2increased linearly as CO2rose from 31 ± 5 to 51 ± 5 Torr. DIA and PCA EMGs also had proportional and comparable increases throughout rebreathing. In contrast, both GG and AN responses differed from the DIA and PCA (P < 0.001) and exhibited minimal or absent responses at low levels of hypercapnia. Consistent GG and AN EMGs appeared at comparable levels of end-tidal CO2(47 ± 5 and 45 ± 5 Torr, respectively) and subsequently increased linearly in most infants. We conclude that during CO2rebreathing the initially delayed and subsequently linear responses of the GG and AN EMGs indicate a high CO2threshold for these muscles.