Pulmonary mechanics are altered in CC16 (club cell secretory protein 16)-deficient mice. Age-matched naive mice either sufficient (wild-type [WT], n = 16) or deficient in CC16 (CC16−/−; n = 16) were assessed using a Flexivent device for airway physiology measurements of (A) total airway resistance, (B) tissue damping, and (C) tissue elastance. ***P < 0.001 by Student’s t test. (D) An additional set of age-matched naive male mice either sufficient (WT, n = 17) or deficient in CC16 (CC16−/−, n = 19) were assessed using a Flexivent device for airway physiology measurements during increasing doses of aerosolized methacholine, **P < 0.01, ***P < 0.001 by Student’s t test. Data shown are the mean ± SEM. Ave = average; G = tissue damping; H = tissue elastance; Rt = total airway resistance.