A new technique has been developed to determine in vivo airway compliance in humans that is specific to airway size and transpulmonary pressure, and can be represented as a three-dimensional surface. As yet, the ability of this technique to detect changes in specific airway compliance with disease status has not been demonstrated. The aim of this study was to assess whether this technique could determine changes in airway compliance which are thought to occur with altered smooth muscle tone in adults with asthma. Airway compliance was measured and displayed as a surface in adults with asthma before and after a reduction in smooth muscle tone by bronchodilator administration. Compliance, with respect to airway size, was calculated at three specific lung volumes; functional residual capacity (FRC), total lung capacity (TLC), and midway between FRC and TLC (MID). After bronchodilator, airway compliance increased at FRC and MID in the smaller airways (<3 mm). Furthermore, airway compliance under both conditions was greater in the smaller airways compared to the larger airways. In conclusion, our method may have future utility in assessing changes in airway compliance in respiratory diseases such as asthma.