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Although anatomic and physiologic abnormalities of the upper airway are thought to be important in the pathogenesis of obstructive sleep apnea (OSA), the relative contributions of these factors have not been elucidated. We therefore measured pharyngeal cross-sectional area (PCSA) and pharyngeal air-flow resistance (Rp) in 12 overweight men with severe symptomatic OSA (mean apnea plus hypopnea Index [AHI], 66.9 ± 6.0 events per hour) and in 17 age- and weight-matched control subjects without spontaneous complaints of OSA symptoms (mean AHI, 4.9 ± 1.6 events per hour). During wakefulness, PCSA was assessed during breath cessation at FRC by computed tomography (CT) and Rp by measuring inspiratory air-flow resistance between the choanae and epiglottis. No measure of PCSA differed significantly between patients and control subjects, and only 1 measure of PCSA, minimal pharyngeal area, correlated with AHI in all subjects (r = −0.38, p < 0.05). In contrast, Rp was significantly higher (p < 0.05) in patients (6.9 ± 1.0 cm H2O/L/s) than in all control subjects (4.2 ± 0.5 cm H2O/L/s) and correlated significantly with AHI (r = 0.53, p < 0.01). We conclude that increased inspiratory resistance to air flow in the naso-oropharynx is present during wakefulness in overweight men with OSA, when compared with matched control subjects without symptomatic OSA, and is associated with disordered breathing during sleep. This occurs even though computed tomography is unable to demonstrate that pharyngeal size during wakefulness at FRC is significantly different between patients and control subjects. These observations suggest that the ability to dilate the pharynx during inspiration may be defective in patients With OSA.