We have investigated the time course of ventilation-perfusion (VA/Q) mismatch and airflow obstruction in 18 patients with acute severe asthma with the objective to identify potential differences according to the clinical severity of the attacks. Nine patients were hospitalized and nine were discharged (emergency room stay < 24 h) according to the clinical criteria of the attending physicians. Spirometry and VA/Q inequality (multiple inert gas technique) were measured within the first 6 h of treatment in the emergency room, and at Weeks 1,2,3, and 4 thereafter. In the emergency room [corrected] hospitalized patients (in relation to those discharged) showed lower airflow rates (FEV1, 31 +/- 3 versus 46 +/- 6% predicted SEM) and greater VA/Q mismatch (as assessed by the dispersion of blood flow distributions (logSD Q) (1.28 +/- 0.11 versus 0.92 +/- 0.11; normal values < 0.6). Even though the rate of improvement of airflow was similar in both groups (without returning to normal limits), VA/Q relationships improved at different rates in each group and reached normal values at the end of the study. Although in hospitalized patients the recovery of VA/Q abnormalities was delayed in relation to airflow rates, the time course in discharged patients was the same. Previous studies have shown a dissociation between spirometry and VA/Q inequality, suggesting that whereas airflow rates predominantly reflect bronchoconstriction of large airways, VA/Q mismatch is more related to obstructive changes in peripheral airways. Our results support this hypothesis and suggest that the more severe the asthma attacks, the more severe the obstructive changes involving peripheral airways for a given degree of widespread airway narrowing.