Adequate pleural drainage is believed to be an essential component of the management of low pH-low glucose parapneumonic effusion. Parapneumonic effusions may become loculated rapidly, preventing adequate drainage with a single chest tube. Administration of intrapleural streptokinase may be effective in promoting drainage for loculated, nonpurulent low pH-low glucose parapneumonic effusions when fibrin adhesions may not yet be organized. Intrapleural streptokinase was used in 12 patients with relatively large, symptomatic, loculated, nonpurulent parapneumonic effusions in whom the initial thoracentesis demonstrated a pH ≤ 7.0 and/or glucose ≤ 40 mg/dl, and when inadequate drainage was demonstrated roentgenographically despite tube thoracostomy. Mean pleural fluid WBC was 9,750/mm3 (range, 1 to 27 K), and pleural fluid glucose and pH were 33 ± 21 mg/dl and 6.95 ± 0.19, respectively. A solution of streptokinase, 250,000 units in normal saline, was given intrapleurally via the chest tube. Effectiveness of intrapleural streptokinase was assessed radiographically and by monitoring the volume of fluid drained from the chest tube after streptokinase instillation. A greater than 50% improvement in the CXR was seen in nine of 12 patients after intrapleural administration of streptokinase. The volume of fluid out in the first 48 h post-streptokinase was 849 ± 836 ml (range, 100 to 3,000). In addition, clinical improvement (decreased chest discomfort, less dyspnea, or reduced fever) was noted in eight of 12 patients after streptokinase treatment. We conclude that intrapleural administration of streptokinase is an effective adjunct to the management of nonpurulent, loculated parapneumonic effusions that may reduce the need for multiple chest tubes or surgical drainage.