The acute respiratory distress syndrome (ARDS) is a disorder of diffuse lung injury secondary to a wide variety of clinical insults (eg, sepsis) and is manifested by impaired oxygenation, pulmonary edema, and decreased static and dynamic compliance. More recently, airflow resistance has been shown to be increased in humans with ARDS. We designed a prospective, randomized, placebo-controlled, crossover trial to determine the presence and reversibility of increased airflow resistance in ARDS. We studied eight mechanically ventilated patients with ARDS (criteria: PaO2 < or = 70 mm Hg with FIO2 < or = 0.4; diffuse bilateral infiltrates; and pulmonary artery wedge pressure < or = 18 mm Hg). Each was intubated with a No. 8.0 orotracheal tube. We measured dynamic compliance (Cdyn), static compliance (Cstat), airflow resistance across the lungs (RL), shunt fraction (Qs/Qt on FIO2 = 1.0), minute ventilation (VE), PaO2/PAO2, and dead space to tidal volume ratio (VD/VT). Patients were blindly assigned to receive either metaproterenol (1 mL 0.5% in 3 mL saline solution) or saline solution (4 mL) aerosolized over 15 min 6 h apart and in random order so that patients served as their own controls. Metaproterenol significantly reduced RL, peak and plateau airway pressure, and increased Cdyn. Metaproterenol tended to increase PaO2/PAO2, but had no effect on pulmonary shunt or dead space ventilation. We conclude that the increase in airflow resistance of ARDS is substantially reversed by aerosolized metaproterenol without affecting dead space. These data suggest that abnormalities of RL are at lest partially due to bronchospasm.