In 5 mechanically ventilated patients with severe neurological injury (SNI), we measured the respiratory system's flow resistance (Rrs) over a range of inspiratory flows between 0.2 to 2 L/s, at inflation volumes (delta V) ranging from 0.1 to 1 L. Under baseline ventilatory conditions (V = 1 L/s; delta V = 0.95 L), we also partitioned Rrs into airway resistance (Raw) and the additional resistance offered by the tissues of the lung and chest wall (delta Rrs). At all inflation volumes, Rrs decreased hyperbolically with increasing flow but was higher than in normal anesthetized paralyzed subjects (N). At V of 1 L/s and delta V of 0.5 L, Rrs was significantly greater in SNI than in N (7.7 +/- 1.5 v 4.2 +/- 0.5 cm H2O/L/s; P < .01). This discrepancy was due to higher Raw in SNI. Indeed, at V of 1 L/s, Raw (mean +/- SEM) was significantly higher in SNI than in N (4.0 +/- 0.9 v 2.4 +/- 0.2 cm H2O/L/s; P < .001), whereas delta Rrs did not differ significantly. The increased Raw in SNI was due to the fact that these patients were therapeutically hyperventilated (PaCO2 = 30.4 +/- 4.2 mm Hg) and as a result their airways were bronchoconstricted. We conclude that in the intensive care unit setting, hyperventilated patients with severe neurological injury can not be considered to be adequate controls in terms of Rrs and Raw, because hypocapnia induces an increase of Raw and consequently also in Rrs (= Raw+delta Rrs).