IgG Fc receptors (FcγRs, especially FcγRIII) and complement (in particular, C5a anaphylatoxin) are critical effectors of the acute inflammatory response to immune complexes (ICs). However, it is unknown whether and how these two key components can interact with each other in vivo. We use here a mouse model of the acute pulmonary IC hypersensitivity reaction to analyze their potential interaction. FcγRIII and C5aR are coexpressed on alveolar macrophages (AMs), and both FcγRIII and C5aR mutant mice display impaired immune responses. We find that recombinant human C5a (rhC5a) can control inverse expression of various FcγRs, and costimulation of ICs with rhC5a results in strong enhancement of FcγRIII-triggered cellular activation in vitro and in vivo. Moreover, we show here that early IC-induced bioactive C5a, and its interaction with C5aR, causes induction of activating FcγRIII and suppression of inhibitory FcγRII on AMs that appears crucial for efficient cytokine production and neutrophil recruitment in lung pathology. Therefore, C5a, which is a potent chemoattractant, has a broader critical function in regulating the inhibitory/activating FcγRII/III receptor pair to connect complement and FcγR effector pathways in immune inflammation.