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 FEV1 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 (IB), 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 FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)