The effects of breathing depth in attenuating induced bronchoconstriction were studied in 12 healthy subjects. On four separate, randomized occasions, the depth of a series of five breaths taken soon (ϳ1 min) after methacholine (MCh) inhalation was varied from spontaneous tidal volume to lung volumes terminating at ϳ80, ϳ90, and 100% of total lung capacity (TLC). Partial forced expiratory flow at 40% of control forced vital capacity (V part) and residual volume (RV) were measured at control and again at 2, 7, and 11 min after MCh. The decrease in V part and the increase in RV were significantly less when the depth of the five-breath series was progressively increased (P Ͻ 0.001), with a linear relationship. The attenuating effects of deep breaths of any amplitude were significantly greater on RV than V part (P Ͻ 0.01) and lasted as long as 11 min, despite a slight decrease with time when the end-inspiratory lung volume was 100% of TLC. In conclusion, in healthy subjects exposed to MCh, a series of breaths of different depth up to TLC caused a progressive and sustained attenuation of bronchoconstriction. The effects of the depth of the five-breath series were more evident on the RV than on V part, likely due to the different mechanisms that regulate airway closure and expiratory flow limitation. deep breath; airflow obstruction; partial forced expiratory flow; residual volume SEVERAL STUDIES HAVE DOCUMENTED the ability of reversing induced airway narrowing by deep breaths in healthy humans (4, 5, 7, 14, 18, 23-25, 31, 35, 38). This effect has been inferred from the increase in forced expiratory flows or the decrease in airway resistance or residual volume (RV) when a full lung inflation was taken after exposing the airways to a constrictor agent. This phenomenon is basically absent or modest in asthma and chronic obstructive pulmonary disease and may contribute to explain the degree of airway hyperresponsiveness (2,4,5,14,(23)(24)(25). The understanding of the mechanisms regulating airway tone in healthy conditions becomes central to the knowledge of the pathophysiology of obstructive lung diseases. All studies have so far focused on the effects of deep breaths taken to total lung capacity (TLC), but little is known about the effects of submaximal inspirations. The only few studies that addressed this issue were conducted in animals after exposing the airways or isolated airway smooth muscle to a constrictor agent and documented a progressive decrease in airway resistance or decrease in airway smooth muscle force with gradual increments of the depth of lung inflations (11, 32).The present study was conducted in healthy humans to examine the effects on airway function of a series of five breaths of variable depth taken soon after inducing airway narrowing by methacholine (MCh). It was intended to address three main questions. First, is induced airway narrowing progressively attenuated by increasing the amplitude of the breaths, or is there a threshold for the effects of lung inflation to become apparent? Second, f...