Some patients with chronic immune thrombocytopenic purpura have autoantibodies to the platelet glycoprotein IIb/IIIa (GPIIb/IIIa) complex. To determine whether these autoantibodies are directed towards the same or different epitopes, we evaluated the ability of four murine monoclonal anti-GPIIb/IIIa antibodies specific for different epitopes to block autoantibody binding. We noted a variation in blocking patterns among autoantibodies from patients with chronic ITP. In addition, we were able to map the relative epitope locations of both the autoantibodies and the monoclonal antibodies. These data show that the anti-GPIIb/IIIa monoclonal autoantibodies in chronic ITP are directed towards different epitopes.