Levels of the plasmin-alpha 2-plasmin inhibitor complex (PLN-A2PI complex) and alpha 2-plasmin inhibitor (A2PI) were determined by enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies in 59 patients with 66 chronic subdural hematomas (SDH's). Normal concentrations of the PLN-A2PI complex and A2PI in plasma are below 0.8 microgram/ml and 60.5 +/- 16.1 micrograms/ml, respectively (mean +/- 2 standard deviations). The hematoma fluid contained high concentrations of the PLN-A2PI complex (4.58 +/- 2.60 micrograms/ml) and low concentrations of A2PI (10.32 +/- 4.81 micrograms/ml), while both values in the plasma of 12 patients with chronic SDH's were within the normal range. This represents local hyperfibrinolytic activity in the hematoma. Stuporous or comatose patients had higher PLN-A2PI complex levels than did the alert and the drowsy or disoriented patients. The layering type of hematoma as seen on computerized tomography scans showed the highest PLN-A2PI complex levels among five types of hematoma. In the fluid drained postoperatively from the subdural cavities of chronic SDH's, both the PLN-A2PI complex and A2PI levels decreased gradually in healing cases. In two patients with hematoma reaccumulation after surgery, both levels increased. The postoperative increase of the PLN-A2PI complex represents the recurrence of intermittent cycles of fibrinolysis, bleeding, coagulation, and hemostasis in the subdural space.