Heat or alkali-aggregated IgG was found to inhibit C2 production by monocytes, whereas chemically cross-linked IgG and antigen-antibody complexes stimulated C2 synthesis. Chemically cross-linked IgG was shown to inhibit monocyte EA-rosette formation presumably because it blocked monocyte Fc receptors. Furthermore stimulation of C2 synthesis was limited to polymers of the IgG1 and IgG3 subclasses. In contrast, heat-aggregated IgG failed to inhibit monocyte EA-rosette formation significantly, and all the heat-aggregated IgG subclasses inhibited C2 production. It therefore appears that physically aggregated IgG does not bind effectively to Fc receptors. As the effects of physically aggregated IgG C2 production are similar to those of the hydrophobic proteins casein and alkali-denatured human serum albumin (HSA), it is suggested that hydrophobic residues in the aggregates bind preferentially to the lipid component of the cell membrane.