OBJECTIVE To compare the efficacy of adjunctive intrapleural streptokinase (SK) with simple closed chest tube drainage (Drain) in the treatment of empyemas and complicated parapneumonic effusions. METHODS This was a controlled study of 52 patients (mean age, 57 years; 41 men) with pleura space sepsis. Forty patients (77%) had empyema and 12 had complicated parapneumonic effusions. Twenty-nine patients were treated with Drain only while 23 received, in addition, repeated daily SK, 250,000 U in saline solution (mean, 5.3 days). RESULTS The two groups of patients had comparable degrees of peripheral blood leukocytosis, frequency of loculated effusions, pleural fluid pH, and lactate dehydrogenase levels. Infective organisms were isolated in 54% of which 32% were anaerobic and 21% were polymicrobial infections. The incidence of surgical decortication was 17% and mortality was 15%. A significantly larger volume of pleural fluid was drained from patients in the SK treatment group (2.0 [1.5] L) than those in the Drain treatment group (1.0 [1.01] L). There were no significant differences, however, between the two treatment groups in terms of duration before defervescence, duration of hospital stay, the need for surgical intervention, or mortality rates. CONCLUSIONS We conclude that thrombolytic therapy increased the volume of fluid drained from pleural empyemas but did not markedly reduce morbidity and mortality.