Percutaneous drainage of abscesses is an effective treatment, but the success rate is lower for abscesses that have septa and are multilocular. Several clinical and in vitro studies suggest urokinase may be useful in such cases. Our study was designed to determine the safety of urokinase administered into an abscess cavity during the course of percutaneous drainage. Our study included 26 consecutive patients with 31 abscesses treated with percutaneous drainage. Exclusion criteria included age less than 18 or more than 95 years, CNS disorders (e.g., tumor, vascular problems), coagulation impairments, hepatic failure, pregnancy, and abscesses in the spleen, pancreas, or interloop area. Three doses were used: group 1 (nine patients), 1000 IU of urokinase per centimeter of abscess diameter; group 2 (11 patients), 2500 IU of urokinase per centimeter of abscess diameter; and group 3 (nine patients), 5000 IU of urokinase per centimeter of abscess diameter. These doses were administered every 8 hr for 3 days along with percutaneous drainage. Charts were reviewed to determine success and to detect adverse clinical events. Studies included sequential CT scans; serial serum determinations of hematocrit, prothrombin time, partial thromboplastin time, platelet count, fibrinogen levels, and levels of fibrin degradation products; and serial laboratory analysis of purulent material for fibrinogen and fibrin degradation products. Percutaneous drainage was considered successful if no surgical intervention was required. Our results showed no significant change in hematologic studies and no bleeding complications. Analysis of purulent material indicated that urokinase remained active in the abscess milieu. Drainage was successful in seven of 11 patients in group 1, all nine patients in group 2, and 10 of 11 patients in group 3. All eight abscesses with septa were successfully drained. Intracavitary urokinase can be given safely during percutaneous drainage of an abscess, with no associated bleeding complications or changes in coagulation parameters.