We hypothesized that an altered effect of lung inflation on airway caliber may in part explain the isolated volume response to bronchodilators, i.e., an increase of forced vital capacity (FVC) without change in 1-s forced expiratory volume (FEV(1)). Small-airway caliber was measured by high-resolution computed tomography at functional residual capacity and total lung capacity in five chronic obstructive pulmonary disease patients with an isolated increase of FVC (FVC responders) and five with an increase of both FVC and FEV(1) (FVC-FEV(1) responders) after inhalation of salbutamol. In FVC-FEV(1) responders, the airway diameter increased with the cube root of increase in lung volume but was unchanged or even decreased in four of five FVC responders. FVC responders had more severe emphysema, as inferred from lung function and imaging studies, than FVC-FEV(1) responders. We speculate that longitudinal traction or space competition (Verbeken EK, Cauberghs M, and Van de Woestijne KP, J Appl Physiol 81: 2468-2480, 1996) are possible underlying mechanisms. We conclude that the isolated volume response to bronchodilators is associated with severe emphysema and likely results from an altered effect of lung inflation on airway caliber.