C-reactive protein (CRP) is a trace serum protein which elevates up to 1000-fold in concentration in association with inflammation and tissue necrosis. CRP binds with phosphocholine and phosphate esters; initiates reactions of agglutination, opsonization and complement consumption; and precipitates with protamine and synthetic polymers of lysine and arginine, and these reactivities are modulated by calcium and phosphocholine. We now report on the interactions of heparin with these polycations in the absence and presence of CRP, which show marked similarities to reactions between antigen and antibody. Heparin optimally precipitated with the polycations over a narrow range of reactant ratios, peaking at slight anion charge excess. The complexes formed did not dissociate in excess heparin: however, complex formation was significantly depressed when heparin was added in a single dose in excess of the amount required for optimal precipitation. Calcium did not affect the precipitation of heparin with polycation, and heparin did not precipitate with CRP. However, heparin did induce a rapid and efficient dissociation of CRP-polycation precipitates preformed at equivalence, with total release of CRP. Small amounts of heparin augmented precipitation under conditions of polycation excess of CRP, but as heparin levels were increased to amounts needed to reach equivalence with polycation, CRP was resolubilized in favor of the preferred heparin-polycation complexes. Chondroitin sulfate was similar to heparin in its effects upon the CRP-poly-L-arginine (PLA) interaction, while hyaluronic acid enhanced CRP-PLA precipitation at all concentrations tested and DNA had neither augmenting nor solubilizing effects. These data indicate that CRP-polycation interactions are significantly and selectively influenced in the presence of small amounts of heparin and certain other polyanions. This modulatory reactivity may be of importance in the biological reactivities of CRP during episodes of acute inflammation.