Recently we showed that work of breathing was higher in the immediate period after extubation as compared with spontaneous breathing through an endotracheal tube. In this study, we evaluated the glottis and trachea as potential sites of increased airway resistance after extubation. We measured breathing pattern, work of breathing, and pressure time product in eight patients during weaning from mechanical ventilation. We acquired data during pressure support ventilation and spontaneous breathing via the ventilator, with the endotracheal tube in place, and after extubation. During bronchoscopy at the time of extubation, we examined the trachea and measured the cross-sectional area of the glottis. Work of breathing and pressure time product were significantly lower during pressure support ventilation as compared with spontaneous breathing after extubation (0.43 +/- 0.10 vs 1.49 +/- 0.10 J/L and 101 +/- 22 vs 299 +/- 30 cm H2O.s/min, respectively; p < 0.05). However, both indexes were significantly higher after extubation as compared with breathing through the endotracheal tube (1.49 +/- 0.10 vs 0.95 +/- 0.12 J/L, 299 +/- 31 vs 196 +/- 26 cm H2O.s/min respectively; p < 0.05). During bronchoscopy, no tracheal or glottic narrowing was detected. The glottic cross-sectional area was successfully measured in four patients at the onset of inspiration and found to be 140 +/- 15 mm2. This value was larger than the mean cross-sectional area of the endotracheal tubes used in these patients (50 mm2). We conclude that neither tracheal nor laryngeal disease caused the increase in work of breathing after extubation. Our data suggest that upper airway narrowing at a more proximal site, such as the oropharynx or velopharynx may be the cause of the increase in respiratory work.