To determine whether asthmatic subjects have an increase in airway wall thickness that could enhance airway narrowing during bronchoprovocation, we examined the relationship between airway responsiveness and bronchial wall thickness measured by high-resolution computed tomography (HRCT), We studied 24 nonsmokers with asthma, of whom 13 had a fixed component of airflow obstruction (Group 1) and 11 had an optimal FEV(1) of 80% or more of the predicted value (Group 2). These subjects were compared with a control group of 10 nonasthmatic subjects (Group 3). Measurements were taken of each subject's expiratory flows, bronchodilator response, lung volumes, and methacholine responsiveness. All subjects used an inhaled beta 2-agonist on demand, and 19 also used inhaled steroids (13 in a Group 1 and six in Group 2). HRCT sections were obtained at the top and base of the lung and at the level of the intermediary bronchus (is), although only this last level was found adequate for analysis. The ratio of IB wall thickness to outer diameter (T/D) showed a negative relationship with the outer diameter in Group 1 only. The mean T/D ratio of IB was not significantly different in Groups 1, 2, and 3, with respective values of 0.16 +/- 0.01, 0.15 +/- 0.01, and 0.18 +/- 0.01 at TLC, and 0.16 +/- 0.01, 0.20 +/- 0.01, and 0.19 +/- 0.01 at FRC. In subjects with a fixed component of airflow obstruction, the thicker the airway wall in relation to its diameter, the lower was the PC20 for methacholine. This was not observed in the other study groups. No correlation was found between the T/D ratio and baseline FEV(1). A correlation was found between the methacholine PC20 and bronchial diameter in Group 3, and the relationship between these same two measures just failed to be significant in Group 1. In conclusion, we found no significant differences in airway wall thickness between subjects with stable asthma and control subjects. In the group with a fixed component of airflow obstruction, there was a weak negative correlation between the T/D ratio and the outer bronchial diameter or methacholine PC20. Bronchial diameter was correlated with the PC20 for methacholine in normal subjects. This suggests that mechanical properties of the airway wall are probably more important than its thickness per se in influencing airway responsiveness in asthma. However, the thickness of the airway wall may be more relevant in asthmatic subjects with a fixed component of airflow obstruction, whereas bronchial diameter may be a major determinant of airway responsiveness in normal subjects.