Although reduced lung compliance is a hallmark of the adult respiratory distress syndrome (ARDS), the role of increased airflow resistance in this disorder has not been well studied. Because animal models of ARDS show marked increases in airflow resistance and because mediators known to participate in lung parenchymal injury have also been implicated in models of increased airway reactivity, we hypothesized that increased airflow resistance is a major contributor to altered lung mechanics in human ARDS. We studied 10 mechanically ventilated patients with ARDS (criteria: PaO2 less than or equal to 70 mm Hg breathing FIO2 greater than or equal to 0.4; bilateral pulmonary roentgenographic infiltrates; Ppaw less than or equal to 18 mm Hg) measuring dynamic (Cdyn) and static (Cstat) compliance, airflow resistance across the lungs (RL), shunt fraction (QS/QT breathing FIO2 = 1.0), minute ventilation (VE), (a/A)PO2, dead space to tidal volume ratio (VD/VT), airflow (pneumotachograph), transpulmonary pressure (intratracheal pressure minus esophageal pressure) and volume (integrated from flow) at 50 L/min peak flow rate. Airflow resistance was uniformly elevated and averaged six times normal (5.32 +/- 0.92 cm H2O/L/s versus 0.88 +/- 0.08) (p less than 0.05). Cdyn correlated directly with (a/A)PO2. RL correlated with peak pressure, but did not correlate with VE, shunt, (a/A)PO2, or VD/VT. We conclude that increased pulmonary airflow resistance contributes significantly to the altered lung mechanics in ARDS. These data are consistent with studies of animal models of ARDS and long-term survivors of ARDS and may be secondary to tissue factors, airway hyperreactivity, or airway inflammation.