A new protamine sulfate test, using serial dilutions of 1% protamine sulfate in tris buffer, is specific for two fibrinogen derivatives that indicate thrombin generation, fibrin monomers, and fibrin degradation products. It is sensitive to low levels of each. It is insensitive to fibrinogen or fibrinogen degradation products and thus readily distinguishes primary from secondary fibrinolysis. The test is not affected by therapeutic levels of heparin. In clinical experience with this test and the staphylococcal clumping test for fibrinogen-fibrin degradation products no false negative reactions have been encountered in disseminated intravascular coagulation or in acute pulmonary thromboembolism. In 85% of patients with acute deep vein thrombosis the protamine sulfate test was positive. Test results in normal subjects and in patients with a variety of conditions are presented here. The protamine sulfate test is a practical, specific, and sensitive blood test for the exclusion of venous thromboembolic disease and disseminated intravascular coagulation.