Ristocetin was trace-labeled with [3H] by the reductive methylation method. It was shown to agglutinate human platelets in the presence of VIIIR:WF in a manner indistinguishable from unlabeled ristocetin. The binding of the labeled ristocetin to normal and enzyme-modified human platelets was studied both in the presence and absence of VIIIR:WF and at nonagglutinating and agglutinating concentrations of ristocetin. Virtually no difference in [3H]ristocetin binding was seen whether VIIIR:WF was present or not. Platelets treated with chymotrypsin, which destroys their ability to agglutinate to VIIIR:WF and ristocetin, did not bind less ristocetin than did control platelets. A pronounced, direct relationship was found between [3H]ristocetin bound by normal platelets and total ristocetin concentration. This implies that at the higher (agglutinating) concentrations of ristocetin either more binding sites are exposed or, more probably, aggregation of ristocetin occurs.