The present studies provide direct evidence that some patients with chronic immune thrombocytopenic purpura (ITP) have autoantibodies reactive with platelet glycoprotein Ib ( GPIb ). Microtiter wells coated with a monoclonal antibody that recognized GPIb were reacted with either platelet extract or a control cell extract. After washing and incubating with test plasma, well-bound IgG was quantitated using radioactive anti-IgG. When compared to plasma from normal subjects, plasma from 3 of 106 patients with chronic ITP had significantly increased quantities of IgG bound to microtiter wells reacted with platelet extracts. Negative results were obtained with the remaining 103 patients with chronic ITP and 59 patients with a variety of other platelet disorders. Plasma from two of the three positive patients precipitated a protein from 125I-surface-labeled platelet extract with a molecular weight similar to GPlb . One of the three patients with anti- GPlb antibody also had demonstrable autoantibodies to the platelet glycoprotein llb / llla complex.