A proposal is made to extract and purify plasminogen activators from human tumors grown in the host and to establish their relationship to a) activators extracted from normal human tissues, b) human urokinase, c) human plasma activator, and d) activator isolated from cultures of human malignant cell lines. The aim of this investigation it to provide the basis on which to judge the relevance to human disease of a rapidly growing volume of information concerning the production of a plasminogen activator by malignantly transformed cells in culture. The basic observation has now been confirmed in many cell lines, and a host of experimental results have been reported concerning a) the effects of externally added proteases on cells in culture, and b) the effect of protease inhibitors on such cells. While this literature is of the greatest potential significance, this applicant feels that the full relevance of this material to human pathology can only be established if it can be shown that 1. plasminogen activators are regular constituents of human tumors; 2. they are produced in greater quantities there than in corresponding normal tissues; and 3. they are related to the activators elaborated by cells in culture upon malignant transformation. Except for a few isolated cases, to date no serious effort has been made to look at the activators in tumors grown in the host, and to answer any of these questions. The present application tries to fill in this gap. The proposed work consists of extracting and purifying activators from surgically removed tumors of the prostate, colon, breast, and lung, as well as from normal prostate and heart obtained from autopsy material. Purification should not be very difficult, since tissue activators appear to be quite stable enzymes. The activators will be compared with each other and with the above mentioned activators on the basis of their substrate specificity, sensitivity to inhibitors, and the kinetics of their plasminogen activating function, but most importantly, by their structural similarities, as judged on the basis of radioimmune assay.