Antibodies (Ab) administered in complex with antigens (Ag) have the capacity to regulate the out-coming specific immune response. Primary immunization with complexes of bovine serum albumin-2,4,6-trinitrophenyl (BSA-TNP) and immunoglobulin (Ig)G2a anti-TNP induced a significant enhancement of IgG1 and IgG2a BSA-specific Ab response compared to immunization with the Ag alone. Enhancement was absent in nude mice, demonstrating the requirement of T cells for this regulation. Secondary immunization with BSA alone in mice previously primed with BSA-TNP/IgG2a led to a dramatic increase of Ab production, showing that immune complexes are efficient inducers of immunological memory. IgG-mediated enhancement of Ab responses has previously been shown to be impaired in mice lacking FcgammaRI, FcgammaRIII and FcepsilonRI owing to gene targeting of the common FcRgamma subunit (FcRgamma-/-). Here we show that enhancement after immunization with BSA-TNP/IgG2a complexes is restored in irradiated FcRgamma-/- recipients transferred with wild-type (FcRgamma+/+) bone marrow (BM) cells. In contrast, no enhancement is seen in FcRgamma+/+ irradiated animals reconstituted with FcRgamma-/- BM cells. We conclude that IgG2a-mediated enhancement of Ab responses is dependent on the presence of FcgammaRI and/or FcgammaRIII on BM-derived cells and that the presence of these receptors on the radioresistant follicular dendritic cell is not essential.