We have developed a simple screening assay for evaluating the global activity of the protein C/protein S system. The new test consists of measuring the prothrombin time (PT) with bovine thromboplastin before and after activation of the PC present in the plasma sample by PROTAC, derived from Agkistrodon contortrix contortrix snake venom. Prolongation of the PT was directly related to the activity of the PC/PS system. One hundred and nineteen thrombophilic patients including 36 with PC deficiency, 22 with PS defect, 35 with APC resistance and 26 with other genetic defects predisposing to thrombosis were tested with the new assay together with 112 healthy subjects. The new test showed a high sensitivity for detection of inherited defects related to the PC/PS system (92%, 91% and 97% for PC defects, PS defects and APC resistance, respectively). Since it can be performed automatically the test could be used to screen for patients predisposed to thrombosis due to impairment of the PC/PS system and those patients who might eventually require more extensive evaluation of the PC/PS system by single component assays.