The effects of continuous positive airway pressure (CPAP) on supraglottic and total pulmonary resistance were determined in 10 healthy premature infants (postconceptional age 34 +/- 2 wk, weight at study 1,628 +/- 250 g). Nasal airflow was measured with a mask pneumotachograph, and pressures in the esophagus and oropharynx were measured with a 5-Fr Millar or fluid-filled catheter. Nasal CPAP between 0 and 5 cmH2O correlated well with oropharyngeal pressure (r = 0.94). Total supraglottic resistance, total pulmonary resistance, and supraglottic resistance in inspiration and expiration were measured on increasing CPAP. Total supraglottic resistance decreased from 46 +/- 29 to 17 +/- 16 cmH2O.l-1.s (P less than 0.005) between 0 and 5 cmH2O CPAP, and a delay in return of resistance to control values was seen as CPAP was reciprocally decreased to 0. CPAP produced a decrease in supraglottic resistance in both inspiration and expiration, from 41 +/- 26 to 14 +/- 9 and from 33 +/- 17 to 10 +/- 6 cmH2O.l-1.s, respectively (P less than 0.01). Total pulmonary resistance also decreased from 161 +/- 40 to 95 +/- 24 cmH2O.l-1.s (P less than 0.01) between 0 and 5 cmH2O CPAP. The decrease in total supraglottic resistance in these infants accounted for 60% of the change in total pulmonary resistance, which occurred on CPAP of 5 cmH2O. We speculate that CPAP may decrease supraglottic resistance directly through mechanical splinting of the airway. This effect of CPAP may be the primary mechanism by which this form of therapy reduces apnea with an obstructive component in premature infants.