An acquired platelet functional defect was found to be present in eight patients who presented with various clinical conditions--three with renal allograft rejection, three with the hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, one with acute consumption coagulopathy due to an incompatible transfusion and one with systemic lupus erythematosus. They showed defective platelet aggregation and reduced levels of adenine nucleotides and serotonin with abnormal uptake and storage of the amine. The bleeding time was more prolonged than predicted from the platelet count. These abnormalities were strikingly similar to those occurring in patients with congenital storage pool deficiency. The acquired defect is thought to be related to the presence in the circulation of "exhausted" platelets following their in vivo exposure to inducers of the release reaction such as damaged endothelium, thrombin and immune complexes. The bleeding tendency of the underlying diseases might be aggravated by the impairment of platelet function.