Fibrin deposition during secondary peritonitis predisposes to abscess formation by protecting bacteria from host-defence mechanisms. To test the hypothesis that local fibrinolytic therapy can prevent the formation of intra-abdominal abscess, daily injections of the fibrinolytic enzymes trypsin and tissue plasminogen activator (t-PA) were administered intraperitoneally to Wistar rats inoculated intraperitoneally with infected fibrin clots. After 5 days, trypsin (1 mg/ml) had significantly (p less than 0.001) reduced abscess formation in animals inoculated with monomicrobial Bacteroides fragilis clots (20% versus 87%) or mixed Escherichia coli-B. fragilis clots (11% versus 91%). Bacteroides fragilis abscesses were also completely prevented with t-PA (0.25 mg/ml). The number of B. fragilis organisms present in residual abscesses in the trypsin-treated group was significantly (p less than 0.05) lower than in the control group (8.2 +/- 0.2, n = 7 versus 5.7 +/- 1.4, n = 4, log CFU/g abscess). In-vitro studies demonstrated that trypsin had no bactericidal effect on B. fragilis, suggesting enhanced clearance of bacteria. From these studies it appears that controlled fibrinolysis at operation may be a useful adjunct to surgery and systemic antibiotics in preventing abscess formation postoperatively.