The capacity to trap immune complexes (IC) was examined using purified peroxidase-antiperoxidase IgG on frozen sections of mouse spleen. In the absence of serum, binding of IC was confined to macrophages in the red pulp. However, when IC were applied in the presence of fresh mouse serum as a source of complement, trapping occurred on follicular dendritic cells (FDC) in the primary follicles. Trapping was specifically inhibited with monoclonal antibodies against complement receptor type 1 (CR1) (8C12) and CR 1/2 (7G6), but not with anti-CR3 (Mac-1). The binding mechanism of IC in the secondary follicles of animals immunized with sheep red blood cells differed from that observed in unimmunized mice. Here, trapping occurred both in the absence and presence of fresh mouse serum. In the absence of fresh mouse serum, trapping on FDC was mediated by FcR gamma II, as demonstrated by blocking with monoclonal antibody 2.4G2. FcR gamma II-mediated trapping was only observed on a relatively small proportion of FDC that was located in the light zone of the secondary follicles, while complement receptor-mediated IC trapping was observed in more expanding areas, including dark zone and corona. These results show that both complement receptor as well as Fc receptor can function in the binding of IC to FDC. They also provide evidence for the existence of functionally different FDC populations in the secondary lymphoid follicles of mouse spleen.