Clumping reaction, using standard suspension of Staph. aureus Newman D-2-C strain and various substrates, was quantitatively tested. It has been shown that clumping occurs in fibrin lysate containing soluble fibrin monomer complexes unclottable by thrombin. The reaction was positive with staphylococcal strains possessing clumping factor regardless of staphylocoagulase production. Clumping reaction is similar to paracoagulation reaction induced by protamine sulfate. The substrate for both reactions is stable at 56 degrees C but is destroyed at 60 degrees C. The kinetics of substrate formation for both reactions during fibrin clot lysis is also similar. Clumping reaction with a strain of Staph. epidermidis possessing no clumping factor was positive when these bacteria were coated with protamine sulfate. The effect of heparin, sodium citrate, urea, 2-mercaptoethanol, merthiolate, and mucin on both reactions was tested. The present findings explain the clumping reaction in serum and emphasize the role of blood clotting and fibrinolytic systems in this phenomenon.