Monoclinic calcium pyrophosphate dihydrate (m-CPPD) crystals were synthesized and characterized using physical methods, IgG binding to m-CPPD crystals was quantitated, and the effect of IgG or plasma opsonization on m-CPPD-induced neutrophil activation was determined. Adsorption of IgG to crystals was measured using fluorescent-labelled FITC-IgG. Neutrophil activation by uncoated m-CPPD and crystals precoated with IgG or plasma was measured using luminol-enhanced chemiluminescence, superoxide anion generation, and myeloperoxidase release. m-CPPD bound small (compared to triclinic CPPD) but significant amounts of IgG and induced a strong activation of neutrophils at low concentrations of crystals. The rate and extent of chemiluminescence, superoxide anion production, and degranulation was not affected by precoating m-CPPD crystals with IgG during the early phase of neutrophil responses, but was inhibited by the precoating of crystals with plasma.