Drs Corcoran and Rahman1 emphasized that clinical use of a therapeutic agent should be determined by its risk/benefit profile. Let us consider the risk/benefit profile of intrapleural fibrinolytics. Because streptokinase and urokinase are not currently available in the United States, we will focus on the tissue plasminogen activator (tPA). Use of tPA is associated with the risk of bleeding. In a retrospective review, four of 57 patients (7%) treated with intrapleural tPA for a parapneumonic effusion (PPE) or empyema experienced bleeding complications, some of which were serious.2 Balanced against the bleeding risk with tPA, clinicians should appreciate that Rahman et al3 concluded in the second Multicenter Intrapleural Sepsis Trial (MIST2) that intrapleural administration of tPA alone was ineffective. Besides the lack of clinical benefit with tPA in this study, there was no difference in the change in intrapleural opacification between placebo and tPA. This observation indicates that tPA did not effectively cause intrapleural fibrinolysis and pleural drainage when used at an empirical intrapleural dose of 10 mg. With possible risk but no evident benefit, we do not favor routine administration of intrapleural fibrinolytics to adults with a PPE requiring drainage.