We conducted a prospective pilot phase I/II clinical trial to evaluate the toxicity and response rate of the chimeric anti-CD20 monoclonal antibody, rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceutical Corporation, San Diego, CA), in the treatment of patients with immune thrombocytopenic purpura. Patients with a clinical diagnosis of idiopathic thrombocytopenic purpura who had failed corticosteroid therapy and whose platelet count was less than 75,000/microL were eligible for the study. Rituximab was administered in a dose-escalation fashion using doses ranging from 50 to 375 mg/m2 weekly for 4 weeks. Thirteen patients have been enrolled on the trial to date and 12 have completed the full course of treatment. No unusual toxicity was noted in this patient population. None of the three patients at the lowest dose level achieved a clinical response. Three of nine patients (30%) who have received rituximab at doses close or equal to the full dose have shown an objective clinical response (two complete responses, one partial response). The study is currently ongoing, and conclusions regarding the overall response rate, clinical parameters that influence response, surrogate markers of response, and the underlying mechanism of response remain to be addressed. The current study should provide answers to a number of important questions regarding the role of rituximab in the treatment of this and other autoimmune disorders.