Immune thrombocytopenic purpura (ITP) is a disorder caused by accelerated destruction of antibody-coated platelets in the reticuloendothelial system (RES), especially the spleen. Inhibition of RES function following intravenous administration of high-dose immunoglobulin G (IVIG) or intravenous anti-D leads to rapid, albeit usually temporary, reversal of thrombocytopenia in the majority of children and adults with ITP. In emergency situations high-dose IVIG is preferred over anti-D because of the more rapid rate of platelet response; for maintenance therapy in Rh positive ITP patients (e.g. children with chronic ITP pre-splenectomy) anti-D is preferred because of its comparable efficacy to IVIG plus ease of administration and lower cost. In children with typical acute ITP and platelet counts < 20 x 10(9)/L IVIG is preferred over anti-D; however other approaches in this patient cohort should be considered before high-dose IVIG, specifically careful observation alone with therapy given only to children with clinically significant haemorrhage or short course oral prednisone at a starting dose of approximately 4 mg/kg/day. Studies are required to define the short and longer term effects of both IVIG and anti-D on the immune system in order to plan more rational use of these immunomodulatory therapies in this model autoimmune disorder.