Increased (more positive) end-expiratory and decreased (more negative) end-inspiratory values for intrapleural pressure (PpI) invariably accompany acute bronchoconstriction. We hypothesize that both the increase in vital capacity (VC) and the decrease in residual volume (RV) observed after dilation of the central airways in patients with reversible obstruction of the airways result, in part, from a restoration of normal PpI during unforced exhalation. To test this hypothesis, we examined the end-expiratory PpI during breathing at rest in ten emphysematous and eight asthmatic subjects before and after inhalation of isoproterenol. The VC increased by 0.38 L after therapy, and the specific airway resistance and the RV decreased by 6.8 cm H2O.sec and 0.63 L, respectively. Total lung capacity was unchanged. The response of the VC to administration of isoproterenol is an important sequel to dilation of the large airways. Bronchioles close at a critical PpI during exhalation. Because PpI normalizes with administration of isoproterenol, this closure may be delayed to a lower pulmonary volume even if improvement in the function of peripheral airways does not occur.