We compared the effectiveness of intrapleural urokinase versus normal saline via a thoracostomy tube in the treatment of parapneumonic empyema in a randomised controlled study. Forty-nine patients with parapneumonic empyema were randomly assigned to receive either intrapleural urokinase or normal saline treatment. The daily volume instilled through a chest tube was 100 ml in both groups. Urokinase (100,000 IU/day) was diluted in normal saline before instillation. The mean duration for defervescence was shorter (7 +/- 3 vs 13 +/- 5 days, p <0.01) and the mean volume of drained fluid during the five-day treatment period was significantly greater in the urokinase group (1.8 +/- 1.5 vs 0.8 +/- 0.8 litres, p <0.001) than in the control group. The subsequent decortication rate was 60% and 29.1%, respectively (p <0.001). The duration of hospitalisation was also shorter in the urokinase group (14 +/- 4 vs 21 +/- 4 days, p <0.001) than in the saline group. We conclude that intrapleural instillation of urokinase in the management of parapneumonic empyema provides a better outcome and reduces the need for decortication.