Soluble immune complexes (ICs) are abundant in autoimmune diseases, yet neutrophil responses to these soluble humoral factors remain uncharacterized. Moreover, the individual role of the uniquely human Fc?RIIA and glycophosphatidylinositol (GPI)-linked Fc?RIIIB in IC-mediated inflammation is still debated. Here we exploited mice and cell lines expressing these human neutrophil Fc?Rs to demonstrate that Fc?RIIIB alone, in the absence of its known signaling partners Fc?RIIA and the integrin Mac-1, internalizes soluble ICs through a mechanism used by GPI-anchored receptors and fluid-phase endocytosis. Fc?RIIA also uses this pathway. As shown by intravital microscopy, Fc?RIIA but not Fc?RIIIB-mediated neutrophil interactions with extravascular soluble ICs results in the formation of neutrophil extracellular traps (NETs) in tissues. Unexpectedly, in wild-type mice, IC-induced NETosis does not rely on the NADPH oxidase, myeloperoxidase, or neutrophil elastase. In the context of soluble ICs present primarily within vessels, Fc?RIIIB-mediated neutrophil recruitment requires Mac-1 and is associated with the removal of intravascular IC deposits. Collectively, our studies assign a new role for Fc?RIIIB in the removal of soluble ICs within the vasculature that may serve to maintain homeostasis, whereas Fc?RIIA engagement of tissue soluble ICs generates NETs, a proinflammatory process linked to autoimmunity.