The hemostatic abnormalities in patients with uremia are related to acquired functional platelet defects. Evidence derived from dialysis, in vitro studies with cell-free uremic plasma, and the ingestion or infusion of uremic metabolities indicate that one or more dialyzable toxins are responsible for altering the function of intrinsically normal platelets. Urea, creatinine, methylguanidine, phenol and phenolic acids, and guanidinosuccinic acid (GSA) have been proposed for this role. These substances affect platelet aggregation, platelet factor 3 activation induced by adenosine diphosphate (ADP), platelet ultrastructure, and bleeding time. Only guanidinosuccinic acid and perhaps the phenolic compounds thus far meet the most rigid criteria for toxins affecting platelet function. A toxin which competitively limits internal platelet transformation in response to exogenous adenosine diphosphate could account for the hemostatic abnormalities found in renal failure.