An enzyme-linked immunosorbent assay and western immunoblotting analysis were used to detect anti-platelet antibodies in the sera of 50 patients with systemic sclerosis. Eleven (22%) positive sera were found by ELISA. Serial investigations showed that the presence of these antibodies was often transient. Immunoblotting analysis demonstrated that the antibodies were directed against a 114 kDa antigen. Using monoclonal antibody, anti-platelet antibodies directed against gpIIIa were found in 4 cases. Similar to immune thrombocytopenia and lupus erythematosus, a significant portion of the anti-platelet antibodies were also directed against the glycoprotein complex IIb/IIIa in systemic sclerosis.