Adult chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder manifested by thrombocytopenia from the effects of antiplatelet autoantibodies and T lymphocyte-mediated platelet cytotoxicity. Multiple studies show that corticosteroid treatment and splenectomy, alone or together, increase platelet counts to safe levels in 60% to 70% of patients. However, there is little information on the outcomes of ITP patients refractory to splenectomy. We studied 114 patients with ITP for whom splenectomy failed and who required additional therapy; long-term follow-up was available on 105 (92%) patients. Seventy-five (71.4%) patients attained stable partial (platelet count greater than 30 x 10(9)/L) or complete (normal platelet count) remission; 51 patients remained in remission after therapy was discontinued, whereas 24 patients required continued treatment. Median time to remission after splenectomy failure was 46 months (range, 1-437 months). Median remission durations were 60 months (range, 10-212 months) for patients off therapy and 48 months (range, 2-167 months) for patients on therapy. Thirty (29.6%) patients remained unresponsive to treatment. Thirty-two patients died, 17 (15.7%) of ITP (bleeding, 11 patients; therapy complications, 6 patients) and 15 (13.9%) of unrelated causes. We conclude that most patients with refractory ITP attain stable remission, though on average this occurs slowly. However, a subpopulation with severe, resistant disease experiences significant morbidity and mortality.