Platelet-directed antibodies and circulating immune complexes (CIC) were removed from plasma of patients with human immunodeficiency virus (HIV) infection and idiopathic thrombocytopenic purpura (ITP) by extracorporeal immunoadsorption using columns of Staphylococcal protein A-silica (Prosorba columns). In addition, stimulation of a broadly cross-reactive anti-F(ab')2 antibody response was observed. These antibodies also appeared to play a role in the additional removal of platelet-directed immunoglobulins (Igs) and CIC from plasma. Removal of these components from plasma was associated with diminishing levels of antibodies and CIC on patient platelets and significant increases in platelet counts. Extracorporeal immunoadsorption of IgG and CIC from plasma is a beneficial new treatment modality for HIV-associated ITP.