Antiplatelet antibodies in chronic idiopathic thrombocytopenic purpura (ITP) mainly target glycoprotein (GP) IIb/IIIa and GPIb/IX. Previous studies, employing modern antigen-specific assays, indicate that serum reactive with both GPIIb/IIIa and GPIb/IX is not an uncommon finding in chronic ITP. However, the mechanism behind this dual reactivity remains unclear. We studied sera from 72 patients with chronic ITP using modified GPIIb/IIIa- and GPIb/IX-specific MAIPA assays. Among the 34 positive sera, seven showed strong reactivity against both GPIIb/IIIa and GPIb/IX. These seven dual reactive ITP sera were further analysed by absorption studies. It was found that sera absorbed with immobilized GPIb/IX lost nearly all serum IgG specific for GPIb/IX but fully retained the IgG specific for GPIIb/IIIa. Conversely, sera absorbed with immobilized GPIIb/IIIa retained their reactivity only with GPIb/IX. These findings demonstrate that ITP sera, reactive with both GPIIb/IIIa and GPIb/IX, contain at least two different IgG antibody populations, each reactive with only one of the GP complexes.