It is well-known that uremic patients present prolonged bleeding times as a common complication. Factors responsible for this disorder have been extensively investigated. In order to elucidate the possible role of uremic middle molecules as responsible for the bleeding tendency observed in uremia, we have studied the effect on platelet aggregation of middle molecules obtained from uremic plasma by Sephadex and ion-exchange chromatography. Our results show that some purified middle molecular fractions have a specific inhibitory activity on platelet aggregation and suggest an important role for these compounds in the pathogenesis of uremic bleeding.