Forty-one patients with thrombotic thrombocytopenic purpura were treated at the Hospital of the University of Pennsylvania, Philadelphia, between 1975 and 1985. Initially, early splenectomy was performed. However, since 1981, more intensive plasma exchange therapy (increase in frequency and size of exchange) has been used as the primary modality of treatment for this disorder. A reduction of the mortality rate over time has been observed. For the period 1975 to 1980, the mortality rate was 41% (seven of 17). In contrast, for the period 1981 to 1985, the mortality rate decreased to 17% (four of 24). These observations support the concept that the initial management of thrombotic thrombocytopenic purpura with intensive daily plasma exchange is associated with improved survival. The role of platelet inhibitors and corticosteroids needs yet to be defined.