Immune thrombocytopenia is a well-recognized part of the clinical spectrum of infection with the human immunodeficiency virus. From November 1985 to February 1988, 15 patients who were human immunodeficiency virus-positive underwent splenectomy for refractory immune thrombocytopenia. Eight patients had thrombocytopenia only, and 7 others were pancytopenic prior to splenectomy. Three of the 15 patients fulfilled criteria for acquired immunodeficiency syndrome before splenectomy, and acquired immunodeficiency syndrome developed in 5 patients during the follow-up period. The median duration of thrombocytopenia prior to surgical therapy was 6 months. A bone marrow biopsy specimen showed hypercellularity with increased megakaryocytes. All patients had a therapeutic response to splenectomy. Long-term remission from thrombocytopenia/pancytopenia was achieved in 14 of the 15 patients during a follow-up period of 2 to 21 months. Splenectomy can be accomplished with an acceptable morbidity. Pneumonia developed postoperatively in 2 patients, but they did not manifest the characteristic picture of overwhelming postsplenectomy sepsis. They had received vaccinations against encapsulated organisms preoperatively. We conclude that splenectomy provides a durable and lasting response for HIV-related thrombocytopenia. Vaccination for Streptococcus pneumonia and Haemophilus influenzae should be given prior to splenectomy although its efficacy is not clear in this group.