This chapter deals with the discovery and early history of the tissue plasminogen activator. The development of fibrinolytic activity in blood will be touched upon only in so far as it relates to questions involving the tissue plasminogen activator. Liver tissue had an inhibiting influence on the fibrinolysins, a finding which the authors associate with the observation that exclusion of the liver from the circulation enhances the fibrinolytic processes in blood. The subcultivation of cells from malignant tissues turned out to be technically more difficult than the cultivation of cells from normal tissues. It was found that explants from malignant tumours tended to liquefy the plasma clot so extensively that further growth ceased. One possibility was that proteolytic enzymes were released from the cells during cultivation. Another possibility under discussion was an effect of enzymes bound to the membrane of the living cell and related to its metabolism.