In the absence of opsonizing antibodies, Bordetella pertussis the causative agent of pertussis, readily binds to phagocytes via complement receptor 3 (CR3). After opsonization with antibodies, binding is mediated by IgG receptors (FcγR). The effect of targeting B. pertussis to either FcγR or CR3 was studied. The fate of unopsonized B. pertussis IgG-opsonized B. pertussis and B. pertussis opsonized with bispecific antibodies (BsAbs) directed to CR3 or FcγRII/-III was compared. IgG antibodies mediated binding and phagocytosis of B. pertussis via FcγR by polymorphonuclear leukocytes (PMNL) in vitro. Opsonization of B. pertussis with BsAbs directed against either CR3 or FcγRII/-III facilitated PMNL phagocytosis; however, in vivo studies with BsAb revealed that FcγR-mediated uptake facilitates B. pertussis clearance, in contrast to uptake via CR3. Targeting of B. pertussis to FcγRII/-III in mice deficient in FcγRII or FcγRIII indicated that the protective effect is attributable to FcγRIII. Competition between uptake via CR3 or FcγR may determine the outcome of natural infection