This study was designed to investigate the pathogenic relevance of platelet-associated autoantibodies in chronic ITP, since the titer of platelet-associated autoantibodies does not appear to correlate with the severity of the disease. Employing a direct immunoprecipitation procedure, we examined platelets from three ITP patients with platelet-associated autoantibodies against GPIIb-IIIa and an unidentified 56 kD protein before and after splenectomy. In two patients, platelet-associated autoantibodies disappeared after splenectomy, and these two patients attained complete remission. In one patient, however, the amount of platelet-associated autoantibodies did not decrease after splenectomy. Although this patient's platelet count transiently increased to 500 x 10(3)/microliters after splenectomy, it decreased to 55 x 10(3)/microliters within a short time. These findings suggest that platelet-associated autoantibodies play a key role in platelet destruction in chronic ITP.