Immune precipitation of bovine serum albumin (BSA) by rabbit anti-BSA antibody (Ab) was studied at 37 degrees C in the presence of normal human serum, normal rabbit serum, decomplemented serum and reagents permitting complement activation either by the classical pathway or the alternative pathway. Inhibition of precipitation occurred in the presence of complement. Antibody-excess complexes were kept soluble more easily than complexes formed at equivalence. Human serum was a better inhibitor than rabbit serum. Analysis of the phenomenon showed that during the first minutes of the reaction immune complexes were maintained in solution by the classical pathway only, but at later stages the alternative pathway was essential. Such soluble immune complexes precipitated after further incubation for 24 hr. The subsequent addition of ethylenediamine tetra-acetate (EDTA) to serum at 37 degrees C holding immune complexes in solution led to a slow aggregation of the complexes. Their size was found to be approximately 25S as assessed by sucrose density-gradient ultracentrifugation and they bore C3 and C4 fragments.