We measured the concentrations of tissue-type plasminogen activator (t-PA) in 92 patients with chronic subdural hematoma involving 102 sites. The t-PA level in the normal plasma was 4.0 +/- 1.8 ng/mL (mean +/- SD), while that in the hematoma content of these patients was 11.2 +/- 6.2 ng/mL. Patients showing stupor (grade 3) and coma (grade 4) had higher t-PA levels than those showing headache (grade 1) and somnolence (grade 2) or psychiatric disorder (grade 5). Also, those with the layer-type hematoma on computed tomographic images had higher t-PA levels than those with any other types. The t-PA level in the draining fluid decreased after surgery. In three patients showing a gradual increase of t-PA, subdural fluid reaccumulated and the general condition remained unchanged after surgery. Overproduction of t-PA is considered to initiate intermittent hemorrhage by conversion of plasminogen to plasmin and results in persistence or enlargement of chronic subdural hematoma.