Many patients with thrombotic thrombocytopenic purpura (TTP) fail to respond to daily plasmapheresis and the results of alternative treatments have been inconsistent. Vincristine was given weekly with continued plasmapheresis to eight patients who were refractory to plasmapheresis, antiplatelet agents, and/or corticosteroids. A rapid response to the vincristine occurred in all eight patients in 5 days with a marked rise in the platelet count and resolution of symptoms. The results in these patients suggest that early initiation of vincristine therapy in conjunction with plasmapheresis is useful in TTP.