Noncommunicating locules of fluid may develop in the setting of a thoracic empyema or a complicated parapneumonic effusion. When this occurs a single chest tube may not provide adequate drainage. In an effort to promote drainage and thereby obviate the need for further procedures, instillation of streptokinase into the involved pleural space has been advocated. This communication reviews the literature and reports our experience with intrapleural streptokinase. In our retrospective review of nine patients, instillation of streptokinase resulted in an obvious increase in chest tube drainage in six. Of the nine patients, four with improved drainage required no further procedures. Two patients with improved drainage and the three with no change in drainage required an additional chest tube, a decortication procedure, or were lost to follow-up. None of the four patients with an empyema were benefitted. Intrapleural instillation of streptokinase may be a useful adjunct in the treatment of a complicated parapneumonic effusion but appears less likely to be of benefit in the management of an empyema.