This study compares the deposition of proteoglycans in the extracellular matrix of the lung lesions of the adult respiratory distress syndrome (ARDS) and bronchiolitis obliterans organizing pneumonia (BOOP) to those present in idiopathic pulmonary fibrosis (IPF). Tissue from individuals with ARDS (n = 7), BOOP (n = 5), IPF (n = 5), and control subjects (n = 5) was examined for glycosaminoglycans and collagen by histochemistry, and for hyaluronan, versican, decorin, biglycan, Types I and III collagen, type I procollagen and alpha-smooth muscle actin (alpha-SMA) using immunohistochemistry. The results showed that glycosaminoglycan deposition in the lesions of ARDS, BOOP, and IPF corresponded to the deposition of versican. Versican localized to the thickened interstitium in the fibroproliferative phase of ARDS, to the intraluminal buds in BOOP, and to early fibroblast foci in IPF. The versican-rich areas contained little mature collagen, but the myofibroblasts in these areas stained for type I procollagen, suggesting early collagen synthesis, and stained intracellularly for decorin. The localization of versican in ARDS, BOOP, and IPF suggests that this proteoglycan may influence early repair processes in the lung.