Eight consecutive patients (mean +/- SD age, 43 +/- 11 yr) with acute severe asthma (status asthmaticus) requiring assisted ventilation were studied within the first 24 to 48 h of admission, at maintenance FIO2 and while breathing 100% O2, using the multiple inert gas elimination technique. Ventilation-perfusion (VA/Q) inequality was characterized by a marked bimodal blood flow distribution (perfusion to normal and low VA/Q populations) in all but two patients, with a mean of 27.6 +/- 12.3% of the total perfusion present in the low VA/Q ratio units (between 0.1 and 0.005). As a result, the dispersion of pulmonary blood flow distribution (log SDQ) was severely abnormal (mean, 1.65 +/- 0.28; normal range, 0.3 to 0.6). No patient had a substantial shunt (VA/Q = 0) (mean value, 1.5 +/- 2.3%). The ventilation distribution was never bimodal, but the dispersion of the ventilation distribution (log SDV) was moderately elevated (1.01 +/- 0.24). High VA/Q areas (ventilation to VA/Q units between 10 and 100) were generally absent. While breathing 100% O2, PaO2, PvO2, and PaCO2 significantly rose, as did shunt and blood flow dispersion. Patients with life-threatening acute severe asthma treated by mechanical ventilation show: (1) the most abnormal gas exchange characteristics of the VA/Q spectrum observed to date in human asthma but essentially the same pattern as in patients with less severe disease; (2) a high level of hypoxic pulmonary vascular response; (3) a significant amount of shunt while breathing 100% O2, suggesting the presence of absorption atelectasis or redistribution of blood flow.