Since recent observations indicate that treatment with high-dose intravenous polyvalent intact immunoglobulin leads to a rapid reversal of thrombocytopenia in the idiopathic thrombocytopenic purpura (ITP) of childhood, we decided to apply this treatment to adults with ITP and to test the possibility that the effect of the immunoglobulin might be attributable to transient blockade of the reticuloendothelial system. Using sequential clearance studies of autologous 99mTc-labeled and anti-Rh(D)-sensitized erythrocytes in four adults with ITP who were treated with total doses of 1 to 1.5 g of immunoglobulin per kilogram of body weight, we found that a transient rise in platelet counts to normal levels within four to five days was accompanied by a marked temporary prolongation of the immune-particle clearance time. These data suggest that commercial intravenous immunoglobulin preparations may interfere with phagocyte Fc-receptor-mediated immune clearance. Since platelets in ITP treated with immunoglobulin were fully hemostatic, this type of therapy may allow surgical procedures to be performed safely in patients with this disease.