Fourteen dogs were studied to determine whether (1) interdependence between airways and parenchyma can limit maximal bronchoconstriction under static conditions in vivo, and (2) stretching of airway smooth muscle during tidal breathing can attenuate muscle shortening and account for the limited bronchoconstriction previously observed in response to increasing doses of methacholine (MCh). In six dogs the left lung was ventilated while 50% MCh was nebulized into the airways of the right lower lobe (RLL) held at constant transpulmonary pressures (PL). Airway closure, as assessed by an alveolar capsule technique during small oscillations in lobar volume, occurred at PL less than or equal to 7.5 cm H2O. To assess the effects of tidal breathing, pulmonary resistance (RL) was measured in four dogs after MCh nebulization into the RLL during tidal breathing while the left lung was separately ventilated. In another four dogs the whole lung was challenged with MCh. At each MCh concentration, RL values in the RLL were much higher than in the whole lungs (30-fold at the highest MCh concentration), showing that maximal bronchoconstriction in response to MCh is much greater in the RLL than in the whole lung. We conclude that neither interdependence nor tidal breathing can fully explain limited maximal bronchoconstriction in living dogs.