Monoclonal antibodies (MAbs) directed against epitopes on the Cγ1, Cγ2, Cγ3 and Cγ2-Cγ3 interface regions of human IgG were used to attempt to localize the monocyte Fc receptor (FcR) binding site. The MAbs have been assayed for their capacity to inhibit the interaction between 125I-labelled IgG (125I-IgG) and human monocytes or human histiocytic lymphoma U937 cells. Two MAbs specific for epitopes on the N-terminal region of the Cγ2 domain, and one MAb recognizing an epitope in the Cγ2-Cγ3 inter-domain region inhibited binding of 125I-IgG to monocyte FcRs. The remaining MAbs, against a C-terminal Cγ3 domain epitope, another Cγ2/Cγ3 region epitope and the Glm(f) allotope on the Cγl domain did not inhibit the interaction. The capacity of the MAbs to bind to their respective epitopes on cell surface FcR-bound IgG was also studied, using indirect radiobinding and immunofluorescence assays. All of the MAbs, except those with Cγ2 domain specificities, were able to detect FcR-bound IgG under these conditions. The results confirm the role of the Cγ2 domain in the interaction of IgG with monocytes and demonstrate that epitopes in the Cγ3 and Cγ2-Cγ3 regions are not involved in the binding site.