We determined the prevalence of antibodies to beta(2) glycoprotein-I (beta(2) GPI) in sera of 57 patients with primary or secondary immune thrombocytopenia positive for platelet antibody (PAIgG) and in 16 healthy control subjects. Both isotypes (IgG and IgM) of anti-beta(2) GPI were detected by means of semiquantitative ELISA and platelet antibodies were measured by means of flow cytometry using FITC-labeled anti-human IgG. Six (10.5%) of 57 patients with immune thrombocytopenia had anti-beta(2) GPI, whereas none of the 16 healthy subjects had anti-beta(2) GPI. Four were positive for IgM anti-beta(2) GPI, one for IgG anti-beta(2) GPI, and one was positive both for IgM and IgG anti-beta(2) GPI. There was no significant association between the presence of anti-beta(2) GPI and the severity of thrombocytopenia. Our findings suggest that some patients with immune thrombocytopenia have anti-beta(2) GPI in addition to the increased PAIgG; however, the results do not support a major role for anti-beta(2) GPI in the pathogenesis of immune thrombocytopenia.