Polyclonal antiserum prepared to purified type I collagen receptor, a 65,000 molecular weight protein, isolated from human platelets reacted with two other proteins with molecular weights of 90,000 and 58,000 in immunoblots of solubilized platelet membranes. The immunoreactive proteins were purified to homogeneity with molecular sieve chromatography and preparative gel electrophoreses. Periodic acid Schiff stain showed that both the 90,000 and 65,000 proteins were glycoproteins. These purified proteins reacted with immunoglobulin G (IgG) fractions isolated from antiserum raised against the 65,000 protein and poly- and monoclonal antibody specific for the glycoprotein IIb-IIIa suggesting that these three proteins are immunocross reactive with GPIIb-IIIa. To further examine the immunocross-reactivity of these proteins, a monoclonal antibody was raised against the 90,000 glycoprotein. This monoclonal antibody also reacted with all three proteins in enzyme-linked immunosorbent assays and transblot experiments suggesting that these three possess a common antigenic determinant. The monoclonal antibody prepared to the 90,000 glycoprotein also inhibited platelet aggregation induced by the addition of collagen and ADP but not alpha-thrombin and epinephrine-induced aggregation. This suggests that the monoclonal antibody binds a protein on the platelet surface which plays a role in platelet aggregation induced by the addition of these agonists.