Neutrophils stimulated with surface-associated monomeric IgG (SAIgG) release an activated collagenase in association with significant generation of hypochlorous acid (HOCl). To determine whether these neutrophil responses are modulated by IgG C fixation, neutrophils were incubated with SAIgG pretreated with normal or C-deficient sera. Treatment of SAIgG with normal sera did not attenuate neutrophil superoxide production, H2O2 generation, or extracellular release of latent collagenase and lactoferrin; however, serum treatment resulted in significant attenuation of SAIgG-induced HOCl generation (75%) and extracellular release of the azurophilic granule constituents myeloperoxidase and cathepsin G. Collagenase activity in supernatants of neutrophils incubated with SAIgG pretreated with normal sera (9.5 ± 0.8 ng/min) was significantly less than activity in supernatants of neutrophils incubated with SAIgG not treated with sera (15.3 ± 1.2 ng/min). Treatment of surface adherent monoclonal IgG1 and IgG2 with sera resulted in significantly greater attenuation of HOCl generation compared to serum treatment of IgG4. Attenuation of HOCl generation was not observed when SAIgG was pretreated with heat-inactivated sera, EDTA-chelated sera, or sera depleted of C3; treatment of SAIgG with C5-depleted sera yielded results comparable to treatment with intact sera. These results indicate that C3- derived ligands fixed to adherent Ig alter IgG-induced release of azurophilic granule constituents and HOCl generation by neutrophils.