Ventilation-perfusion (VA/Q) inequality has been evaluated using the multiple inert gas technique in nine nonsmoking patients (mean +/- SD, age 56 +/- 10 yr) with stable, severe, chronic asthma (partially reversible airway obstruction; baseline FEV1, 39 +/- 10% predicted) before and during 100% O2 breathing and then 15 min after three puffs (300 micrograms) of inhaled salbutamol. The aim of this study was to investigate whether this type of asthma was associated with a different pattern of VA/Q inequality from that observed in acute episodes and in particular to determine whether the VA/Q pattern was fixed or could be altered by bronchodilator agents or O2 breathing. The predominant pattern of VA/Q distribution was broad and unimodal but without shunt (VA/Q = 0) or low VA/Q areas (VA/Q less than 0.1 to greater than 0.005). The amount of VA/Q inequality as assessed by the dispersion of the distribution of pulmonary bloodflow (log SDQ) was not great (log SDQ, 0.77 +/- 0.09), and no correlation was found with the degree of airway obstruction, PaO2 or AaPO2. During 100% O2 breathing, VA/Q inequality worsened (from log SDQ of 0.77 +/- 0.09 to 1.11 +/- 0.21, p = 0.01) with an increase in the perfusion of low VA/Q units (from 0.43 +/- 0.66% to 6.3 +/- 6.5%, p = 0.02) but still no development of shunt. This suggests the presence of hypoxic pulmonary vasoconstriction breathing air, possibly contributing to the preservation of VA/Q relationships.(ABSTRACT TRUNCATED AT 250 WORDS)