We have studied the expression of immunochemically-related membrane proteins on human platelets and human umbilical vein endothelial cells (EC) by using cross-immunoprecipitation of 125I, surface-labeled cell extracts by cell-specific antisera, coupled to one- or two-dimensional SDS-PAGE. From 125I-labeled EC, an anti-platelet antiserum was found to immunoprecipitate major surface polypeptides comigrating with platelet GPIa, GPIIa and GPIIIa, and a protein with relative molecular mass Mr = 54,000. On the other hand, anti-EC antisera precipitated mostly GPIa, GPIc, GPIIa and GPIIIa from 125I-labeled platelets. These results supported previous reports demonstrating shared major membrane glycoproteins on platelets and EC, and suggested that the similar antigenicities in platelets and endothelial cells could play an important role in the pathogenesis of thrombosis and hemostasis in some immunologic disorders.