Fibrin deposition is prominent in the course of several forms of pulmonary fibrosis. To elucidate the role of fibrin deposition and fibrinolysis in the process of pulmonary fibrosis, we studied bleomycin-induced fibrosis and the effect of urokinase on it. Beagle dogs were injected intramuscularly 20 times with bleomycin in doses of 2 and 6 mg/kg body weight every other day. Intravenous urokinase treatment was subsequently performed with 3,000 units daily for 40 days and 9,000 units twice daily for 70 days. Histopathologic examination of the lungs of dogs receiving bleomycin alone revealed fibrosis. The lungs of bleomycin-treated dogs which received urokinase had less severe fibrosis and this was confirmed by morphometry with planimetry and the point counting method. Urokinase treatment also diminished the increase of hydroxyproline content of the lung of bleomycin-treated dogs. Decrease of lung tissue fibrinolytic activity assayed by fibrin plate method in bleomycin-treated dogs was also prevented by urokinase. Intravenous urokinase, 24,000 units per day in divided doses, was administered daily in cancer patients with bleomycin treatment. Incidence of pulmonary fibrosis was decreased by urokinase. These data indicate that fibrin deposition and fibrinolysis may have an important influence on the fibrotic process in the lung.