The purpose of this study was to determine the effect of hyperventilation (40 L/min) with room air (25 degrees C; 70% relative humidity) and frigid air (-10 degrees C; 0% relative humidity) on airway mucosal blood flow (Qaw) in normal subjects (n = 7; 26 to 54 yr of age). Qaw was measured with the dimethyl ether uptake technique, which reflects blood flow in the mucosa of large airways corresponding to a 50-ml anatomic dead space segment extending distally from the trachea. Mean (+/- SE) baseline Qaw during quiet (room air) breathing was 6.6 +/- 0.6 ml/min (range, 3.9 to 10.9). Qaw failed to change significantly during and after eucapnic hyperventilation with room air (thermal stress, 224 cal/min). In contrast, eucapnic hyperventilation with frigid air (thermal stress, 720 cal/min) increased Qaw in every subject, with the peak value occurring either during or over a 30-min period after hyperventilation; by 60 min, Qaw had returned toward baseline. The mean maximal Qaw was 310 +/- 49% of baseline (p < 0.05). Neither type of hyperventilation had an effect on airway resistance. We conclude that in normal subjects, Qaw increases during and/or after eucapnic hyperventilation with frigid air, and that this response is related to the magnitude of the thermal stress rather than to the level of ventilation.