The authors prospectively treated 10 consecutive patients with multiloculated empyemas with intracavitary instillation of urokinase via a percutaneous drainage catheter. Urokinase (100,000 IU) in 100 mL of 5% dextrose in water was instilled into the pleural cavity via a percutaneous drainage catheter. After overnight clamping, the catheter was opened and the empyema drained with use of negative suction (20 cm H2O). Intermittent irrigation of the catheter with normal saline was performed to prevent clogging of the catheter. Complete drainage of multiloculated empyemas was accomplished in nine patients by means of intracavitary instillation of urokinase via a single 8-F catheter. One patient showed complete drainage of multiloculated empyema, but recurrent empyema appeared in the site of a previous tube thoracostomy. A total of 100,000-700,000 IU (mean, 400,000 IU) of urokinase were needed for complete drainage in all patients. Plasminogen and fibrin degradation product levels in empyema fluid were determined before instillation of urokinase to demonstrate any fibrinolytic action. No complications occurred.