In this issue of the JCI, Shushakova et al.(1) describe experimental results that provide a direct link between the C5a anaphylotoxin and the IgG Fc receptors (FcγRs) in mediating immune complex–triggered (IC-triggered) inflammatory disease. Using a murine lung model of IC-induced inflammation, the authors demonstrate that C5a, acting through the C5a receptor (C5aR), exacerbates inflammation in part by altering the ratio of activation to inhibitory FcγR expression on alveolar macrophages, enhancing the former and suppressing the latter, thereby optimizing the ability of alveolar macrophages to respond to ICs and trigger cytokine release and neutrophil chemotaxis. C5a now joins the ranks of other regulators of FcγR expression, such as IFN-γ and intravenous immunoglobulin (IVIG), in modulating IC-induced inflammation by acting on the primary IC targets, the FcγRs. What makes this observation worthy of comment is the historical context of IC-mediated inflammation and the confusion that has surrounded the basic mechanism of this fundamental immunological reaction, the Arthus reaction.