BACKGROUND: Upper-airway function is thought to influence gas exchange and lung volume through an expiratory braking mechanism producing increased subglottic pressures. We designed an experiment to examine the effect of partial upper-airway bypass on the development of subglottic pressure during acute lung injury (ALI). MATERIALS & METHODS: Six healthy adult domestic sheep un-derwent surgical placement of a tracheal Kistner button in the upper trachea and carotid transposition for arterial blood access. On the following day, baseline air-way-pressure tracings were obtained at the Kistner button, and respiratory air-flow tracings were obtained at the mouth. All measurements and recordings were initially made with the Kistner buttons closed to atmosphere, allowing respiration only across the upper airway, and then were repeated with the Kistner buttons open, allowing partial respiratory bypass of the upper airway. Twenty-four hours following the baseline recordings, an intravenous infusion of oleic acid (0.08 mL/ kg) was administered to produce ALI. On the following day, the recordings were repeated and arterial blood gas samples were obtained. RESULTS: Subglottic pressures at baseline with the Kistner buttons closed (3.5 cm H2O [0.34 kPa]) were significantly larger than when the Kistner buttons were open, (1.4 cm H2O [0.14 kPa], p < 0.0001). The respiratory rates, inspiratory times (t1), expiratory times (te), and the ti-to-te ratio (I:E) were unchanged with the Kistner buttons open to atmosphere. With ALI, subglottic pressure was significantly increased (p > 0.0001), compared to baseline (12.3 cm H2O [1.21 kPa] vs cm H2O [0.34 kPa], re-spectively). Other variables demonstrated a decrease in the t1 (p < 0.001) and a de-crease in the I:E (p < 0.0001) compared to baseline measurements. No significant difference existed in te or the respiratory rates. Opening of the Kistner buttons during acute lung injury produced a significant decrease in subglottic pressures (p < 0.0001) and te (p = 0.0031), whereas the t1 and I:E significantly increased with this maneuver (p = 0.0002 and p < 0.0001, respectively). The partial pressures of oxygen were found to be significantly greater (p = 0.0401) with the Kistner buttons closed to atmosphere (64.3 torr [8.58 kPa]) than when they were open (53.5 torr [7.13 kPa]), during ALI. CONCLUSIONS: Our results suggest that (1) partial by-pass of the upper airway may be associated with a decrease in the development of subglottic pressures, and (2) respiratory timing and pulmonary gas exchange are influenced by the upper airway during ALI.