Plasma exchange is of proven efficacy in the treatment of thrombotic thrombocytopenic purpura (TTP). In most series, less than 40 plasma exchanges (PE) were required for treatment and as many as two thirds of patients had permanent residual organ damage. We report on 4 patients who required very intensive PE for the resolution of TTP (37, 68, 102 and 108 procedures, respectively). The maximum number of PE procedures per attack was 102. None of these patients has any permanent sequellae of TTP (other than those associated with splenectomy, which was performed on all patients). Two of the female patients had uncomplicated pregnancies since resolution of the disease. We conclude that even highly refractory cases of TTP can have an excellent clinical outcome with intense PE therapy.