Plasminogen activators are serine proteinases which transform the serum zymogen, plasminogen, into plasmin, a broad-spectrum protease with fibrinolytic effect. Two main plasminogen activators have been described in humans: urokinase (UK; molecular weight, 55,000) and tissue-type plasminogen activator (tPA; molecular weight, 74,000). Thirteen subjects were studied who had alopecia areata (AA), nine in the active phase and four in remission. There were alterations in the perivascular and peribulbar fibrinolytic activity in the nine subjects in the active phase of disease, suggesting a possible role of plasminogen activators in AA. A modified Todd's autohistographic method was used to evaluate cutaneous fibrinolytic activity (which depended on the activity of plasminogen activators) in the 13 AA subjects and five volunteer controls. Cutaneous fibrinolytic activity was reduced in perivascular areas, but increased in peribulbar areas, in the nine subjects in the active phase of disease. Tests with monoclonal antibodies directed against the catalytic sites of tPA and UK showed that the perivascular fibrinolytic activity was tPA dependent, and the peribulbar fibrinolytic activity was UK dependent.