Thrombotic thrombocytopenic purpura (TTP) is a disorder of systemic platelet aggregation. Evidence has accumulated that the aggregating agonist in TTP of all types is likely to be von Willebrand factor (vWf), especially unusually large vWf multimers derived from endothelial cells. Recent evidence indicates that a metalloproteinase involved in vWf breakdown is produced in inadequate amounts in children with chronic relapsing TTP. Chronic relapsing TTP is, therefore, likely to be a congenital enzyme deficiency. In adults with single episode or intermittent types of TTP, the vWf metalloproteinase is inhibited by autoantibodies that are present either transiently or intermittently in patient blood. Single episode and intermittent types of TTP in adults are likely to be short-term or recurrent autoimmune processes, respectively.