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The authors retrospectively review the clinical course and outcome of 6 pediatric patients, ranging in age from 2 to 13 years, who were treated with TPA for complex empye-ma. Efficacy was assessed by evaluating pleural fluid drainage for 6 hours prior to and subsequent to each dose of TPA, as well as by resolution of fever and length of hospital stay. The average volume drained for 6 hours before infusion of TPA was 22.5 mL ± 18.4 mL, and the average volume 6 hours after TPA therapy was 141.7 mL ± 28.3 mL, P < .0001. After initiation of TPA therapy, 5 out of 6 patients became afebrile within 48 hours. The median length of stay after initiation of TPA therapy was 6 days, with a range from 4 days to 12 days. A discussion of other current therapies for empyema, along with a comparison of these therapies to TPA regarding the costs of therapies and risk-benefit ratios, is also included.