Diffuse alveolar damage, clinically represented as acute respiratory distress syndrome, can be idiopathic. But it is more often due to other causes that cover an extensive list and can include infection both bacterial and viral, drugs, collagen vascular disease, inhalants/toxins, shock, and pulmonary vasculitis/pulmonary hemorrhage syndromes (Table 16-1). The lung injury, which is acute, shows similar histologic features regardless of the underlying cause or initiating event. Depending on the time interval of the underlying insult and transbronchial biopsy, the histologic features show variable morphology with an early acute phase, an organizing or proliferative phase, and a late fibrotic phase. The early acute phase is seen on biopsy as interstitial and intra-alveolar edema associated with variable hemorrhage and deposits of fibrin with the characteristic hyaline membranes forming several days after injury. Usually a week after injury the hyaline membranes are well formed and seen as eosinophilic fibrinous material of variable thickness, outlining the intra-alveolar spaces. The proliferative phase is seen at this time (usually 7 days after injury) associated with the hyaline membranes, type II pneumocyte hyperplasia, and demonstrates in the interstitium features of organization with formation of fibroblastic foci and associated acute inflammation. Diffuse alveolar damage can regress with treatment; however progression can also occur with fibrosis characterized by cellular infiltrates with proliferation of fibroblasts and deposition of collagen.