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Pleural effusions and empyemas may complicate 20–57% of bacterial pneumonias. Clinical experience supports the use of fibrinolytic agents as a means of dissolving fibrin, releasing loculations and adhesions, thereby allowing for free drainage via thoracostomy tubes. Currently available thrombolytic agents include urokinase, tissue plasminogen activator (TPA), and streptokinase. Due to manufacturer-related issues, the supply of urokinase has become somewhat limited while streptokinase has the potential for allergic reactions in pediatric patients. The authors report the use of TPA as an adjunct to other therapies for treatment of empyema in a 6-year-old boy with pneumococcal pneumonia.