To evaluate the efficacy and safety of splenectomy in patients with human immunodeficiency virus (HIV)-related thrombocytopenia, 30 HIV-infected patients with thrombocytopenia (platelet count < 50 x 10(9)/l) who underwent splenectomy were followed prospectively for a mean period of 42 months. There were no perioperative deaths and morbidity was minimal. Twenty-one patients had a persistent complete response, six had a partial response and were asymptomatic after splenectomy, and only three showed no response. Three patients developed acquired immune deficiency syndrome during follow-up, an incidence that was no different from that expected. Splenectomy is a safe and effective treatment in HIV-infected patients with severe symptomatic thrombocytopenic purpura resistant to medical therapy.