Broth cultures of hemolytic streptococci derived from patients are capable of rapidly liquefying normal human fibrin clot. The active fibrinolytic principle is also contained in sterile, cell-free filtrates of broth cultures. The degree of activity of filtrates parallels the activity of whole broth cultures sufficiently closely to indicate that large amounts of the fibrinolytic substance are freely excreted into the surrounding medium and pass readily through Berkefeld V, Seitz, and Chamberland filters. The occurrence of fibrinolysis is most strikingly observed when plasma or fibrinogen is mixed with active cultural material before clot formation is effected. Under the standard experimental conditions described, complete dissolution of human plasma clot (whole oxalated plasma + CaCl2) occurs in about 10 minutes; complete dissolution of human fibrinogen clot (chemically isolated fibrinogen + thrombin) takes place in about 2 minutes. Titration of filtrate activity is recorded in Table IV. Twenty-eight strains of Streptococcus hemolyticus, isolated from patients suffering from various manifestations of streptococcus infection, have been tested for the capacity to liquefy fibrin clot. Broth cultures of all of the strains induced fibrinolysis. Of 18 strains of Streptococcus hemolyticus of animal origin, only three were capable of causing dissolution of clot. Completely negative results were obtained with 38 strains of other bacterial species. The list is presented on pages 492 and 493. The plasma of many patients recovered from acute hemolytic streptococcus infections, when clotted in the presence of active cultures, is highly resistant to fibrinolysis. Furthermore, serum, derived from patients whose plasma clot is resistant, often confers on normal plasma clot an antifibrinolytic property. One example of the resistance possessed by the blood of convalescent patients is presented in this report. A second paper, now in preparation, will give in detail a large number of observations on the relation of infection to the development of resistance to the fibrinolytic activity of hemolytic streptococci. In contrast to the susceptibility of normal human fibrin clot to liquefaction by active culture, normal rabbit fibrin clot is totally resistant to dissolution when tested under comparable conditions. The insusceptibility of rabbit fibrin clot is manifest provided the coagulum is composed of rabbit constituents. When human thrombin is used to clot rabbit plasma or fibrinogen in the presence of active cultures, fibrinolysis is not prohibited. The rôle of thrombin in determining the resistance or susceptibility of rabbit fibrin to dissolution offers a suggestive approach to problems relating to the underiving mechanism.