To assess the effects on mononuclear phagocyte function of i.v. γ-globulin treatment in idiopathic thrombocytopenic purpura, we examined in vivo and in vitro mononuclear phagocyte function in 11 patients before and after therapy. All patients, both splenectomized and non-splenectomized, demonstrated a prolongation of in vivo clearance of autologous IgG-sensitized erythrocytes (p < 0.01). Concurrent in vitro assessment of blood monocyte function showed decreased IgG-sensitized erythrocyte (EA) rosette formation (mean ± SD: 31.6% ± 8.2 vs 24.5% ± 9.5; p < 0.03) and decreased affinity of Fc receptor-specific IgG oligomer binding (9.9 ± 16.3 vs 1.8 ± 2.1 x 108 M-1; p < 0.008), but no consistent change in the estimate of the maximum number of binding sites. Phagocytosis of two different EA probes was decreased (EhuA:0.49 ± 0.26 vs 0.25 ± 0.14 erythrocyte/monocyte/hr; p < 0.02, EoxA:1.76 ± 0.66 vs 1.27 ± 0.67 erythrocyte/monocyte/hr, p < 0.05). The change in in vivo mononuclear phagocyte system clearance was significantly correlated with the change in the association constant for oligomer binding (r = 0.98, p < 0.05). These data demonstrate that i.v. γ-globulin infusions induce alterations of mononuclear phagocyte function that are not dependent on the presence of autologous serum containing infusate. The change in apparent Fc receptor affinity rather than receptor number may reflect an altered Fc receptor population with different binding properties.