The effect of nasal airway positive pressure (NAPP) on upper airway size and configuration during wakefulness was studied by computerized tomography in 12 obese subjects with obstructive sleep apnea (OSA), seven weight- and age-matched subjects without OSA, and 12 normal subjects. NAPP of 10 to 12 cm H2O was associated with a significant increase in airway area throughout the upper airway in all three groups. The change in airway area per cm H2O NAPP increased from nasopharynx to hypopharynx. The change in airway area per cm H2O NAPP was significantly smaller in the OSA than in the normal subjects in the region of the soft palate. Electromyographic recordings of the genioglossus and alae nasi muscles with and without NAPP during wakefulness in five of the OSA and five of the normal subjects showed either a decrease or no change in phasic and tonic activity with NAPP. In a separate series of experiments in an additional five OSA and five normal subjects, NAPP of zero, 5, 10, and 15 cm H2O was associated with a linear increase in airway area at a given airway level. These results indicate that (1) the increase in pharyngeal cross-sectional area with application of NAPP during wakefulness is smaller in OSA than in normal subjects in the region of the soft palate and (2) changes in upper airway muscle activity may accompany changes in upper airway size and configuration.