Insoluble precipitates between C-reactive protein and pneumococcal C-polysaccharide were solubilized by fresh but not heat-inactivated human serum. Solubilization was dependent on the C-reactive protein to C-polysaccharide ratio and the serum concentration and proceeded optimally at 37 degrees C. On 12 to 30% sucrose density gradients solubilized complexes sedimented as a broad peak between the 7S region and the bottom of the tube. In C2-deficient human serum, solubilization was delayed by 30 min and then proceeded at a slow rate. Immunoprecipitation experiments indicated that C3, C4, C5, and to a lesser extent C1q were deposited on solubilized complexes. After dissociating solubilized complexes with EDTA, a considerable percentage of C-polysaccharide coprecipitated with C3, C4, and C5, whereas C-reactive protein coprecipitated with only C3. SDS-PAGE analysis of solubilized precipitates indicated the formation of covalent complexes between fragments of C3 and both C-polysaccharide and C-reactive protein.