Severe thrombocytopenia (TP) accounted for 5.3% of cases in a consecutive series of 380 HIV-infected intravenous drug users (IVDUs) at presentation. Forty-one of 53 subjects with severe TP showed haemorrhages and were treated as follows: ten were splenectomized, 17 were given high-dose intravenous immunoglobulins (HDlg), and 10 received anti-Rh(D) immunoglobulins (anti-Rh lg). Splenectomy induced a complete clinical response in all cases: four out of 10 patients maintained platelet counts > 100 x 109/l. HDlg gave a good clinical response in all patients, but eight out of 17 suffered haemorrhages during the follow-up and recall treatments were necessary. Six out of 10 patients treated with anti-Rh lg maintained platelet counts > 30 x 109/l, but in two cases the treatment was interrupted because of severe haemolysis. No patient progressed to overt AIDS during the follow-up. Splenectomized patients in particular did not show adjunctive risks of worsening of the HIV-related clinical picture. A platelet kinetic study performed in 20 patients with severe HIV-related TP suggests a possible role for platelet sequestration in TP of HIV-infected IVDUs, in which a liver involvement is very frequent.