Patients with loculated parapneumonic effusion or empyema are sometimes treated with streptokinase or urokinase in an attempt to facilitate pleural fluid drainage by liquefying the pleural exudate and destroying the fibrin membranes producing the loculation. This study evaluated the effectiveness of streptokinase, urokinase, and Varidase (the combination of streptokinase and streptodornase) in liquefying gummy, purulent, exudative material from loculated empyemas. An empyema was created by injecting 10(8) Pasteurella multocida bacteria into the pleural space of New Zealand white rabbits. Twenty specimens, each containing 0.5 g of purulent material obtained 5 days after empyema induction, were placed in test tubes. Streptokinase (15,000 IU), urokinase (10,000 IU), Varidase (4,000-15,000 IU streptodornase + 15,000 IU streptokinase) or saline was added to five sets of four test tubes each. The amount of nonliquefied material that remained after incubation with the fibrinolytic agents was quantitated. Over the 6-h incubation period, the amount of nonliquefied material decreased from 0.5 g to 0.02 g in the Varidase group but never decreased to less than 0.4 g in any of the other three treatment groups. Liquefaction of thick pleural exudates from rabbits with empyema can be achieved with Varidase but not with streptokinase or urokinase.