In this paper we examine the role of the classical pathway in the complement-mediated solubilization of immune precipitates (CRA). Serum reagents were depleted of the alternative pathway components properdin and factor D. Both depleted reagents lack CRA although they have almost intact hemolytic activity. Also, immune complexes were not solubilized when incubated with high concentrations of the classical pathway components (C1, C4, C2, and C3. We conclude that CRA is not mediated by the classical pathway alone. Activation of the classical pathway by the immune aggregates greatly enhances CRA. The effect of the classical pathway is to deposit C3b on the antigen-antibody lattice and promote the assembly of a lattice-associated, properdin-dependent C3-convertase. Although C3, C4, and properdin were detected on complexes solubilized by serum in the presence of Ca++ and Mg++, only C3 and properdin were found on the complexes when Ca++ had been chelated by ethylene glycol-bis-(beta-aminoethyl ether), N,N'-tetraacetic acid. In both situations the aggregates were capable of converting C5 in the fluid phase. However, no C5 was found on the solubilized complexes. These findings suggest that in contrast to nascent C3b and C4b, nascent C5-9 lacks binding affinity for immune aggregates.