diffuse pulmonary fibrosis is associated with bleomycin administration to humans . 
 the sequential reactions of lung cells to this drug have now been investigated in mice following injection of 20 mg / kg bleomycin twice per week for 4 to 8 weeks . 
 cytoplasmic and subendothelial edema was first observed in large vessels and by 4 weeks involved the capillaries . 
 the reaction in many animals did not progress further than endothelial lesions with accumulation of interstitial edema . 
 however , 30% of mice subsequently showed necrosis of type 1 epithelium with a fibrinous exudate in the alveoli . 
 fibroblastic organization of the fibrin resulted in the deposition of intraalveolar collagen as well as extensive septal fibrosis by 8 weeks . 
 epithelial repair , normally accomplished by type 2 cell proliferation and transformation to type 1 cells , is characterized in this case by division and metaplasia of type 2 cells.the metaplastic cells were , however , capable of dna synthesis and probably of further cell division . 
 the results indicate that the pulmonary endothelium is the initial site of injury 
 . extensive damage to these cells could allow the drug access to interstitial and epithelial cells . 
 focal necrosis of type 1 epithelium is the critical event that triggers the exudation of fibrin and the subsequent reparative processes.imagesfigure 1.figure 2.figure 3.figure 4.figure 5.figure 6 .