Plasma exchange (PE) and intravenous gammaglobulin (IVGG) are potentially effective therapies in immune thrombocytopenic purpura (ITP). In this study, eight patients refractory to IVGG and to prednisone were treated with a protocol of combined PE and IVGG therapy using a single PE on each of 3 consecutive days, followed by 2 consecutive days of IVGG at 1 g per kg. Four of the eight patients responded to the combined therapy with a mean peak platelet count of 132,000 per microliter (range, 74,000 to 225,000/µliter). Responses lasted approximately 2 weeks. These four patients were among the five who had initially responded to IVGG before becoming refractory; none of the three patients without an initial response to IVGG responded to the combined therapy. Age, duration of disease, and splenectomy status did not appear to be related to response to the combined therapy. Two patients began maintenance treatment (1 PE followed by 1 g/kg IVGG on the same day), but both became unresponsive after three treatments. PE combined with IVGG may be a useful treatment for some patients with refractory ITP who have uncontrollable bleeding or require major surgery. The development of resistance to IVGG effect may be mediated by an increase in the level of antiplatelet antibodies. PE, by lowering antiplatelet antibody levels, may then allow IVGG infusion to be effective again in elevating the platelet count.