Decorin (Dcn), a small leucine-rich proteoglycan, is present in the extracellular matrix of the airways and lung tissues, contributes to lung mechanical properties and deposition is altered in asthma. The effect of Dcn deficiency on airway parenchymal interdependence was examined during induced bronchoconstriction. Studies were performed in C57Bl/6 mice, in which the Dcn gene was disrupted by targeted deletion (Dcn -/-) and in wild type controls (Dcn +/+). Mice were mechanically ventilated, and respiratory system impedance (ZRS) measured during in vivo ventilation at PEEP = 2 and 10 cmH₂0, before and after aerosol delivery of methacholine (MCh). Length vs tension curves in isolated tracheal rings were measured in vitro. Dcn distribution in +/+ mice airways was characterized by immunofluorescence; differences in collagen structure in Dcn +/+ and -/- mouse lungs was examined by electron microscopy. MCh caused similar increases in airway resistance (Raw) and tissue elastance (H) in Dcn +/+ and -/- mice. During MCh-induced constriction, increasing PEEP caused a decrease in Raw, which was greater in Dcn -/- mice; and a decrease in H in Dcn -/- mice, only. Tracheal ring compliance was greater in Dcn -/- mice. Imaging studies showed that Dcn was deposited primarily in the airway adventitial layer in Dcn +/+ mice; in Dcn -/- mice, collagen had an irregular appearance, especially in the lung periphery. These results show that lack of Dcn alters the normal interaction between airways and lung parenchyma; in asthma, changes in Dcn could potentially contribute to abnormal airway physiology.