We report 3 children who developed persistent antibody depletion and abnormal response to bacteriophage after rituximab treatment for autoimmune cytopenias. Whether these patients have developed immunodeficiency secondary to an underlying disease process, to rituximab, or both, is not understood. Rituximab is an efficacious drug for a number of pediatric conditions. However, some patients who receive the drug have prolonged suppression or absence of B-cell function. Families should be counseled of this possibility prior to therapy. Patients should have baseline measurement of quantitative immunoglobulins and specific antibody levels and should be monitored for long term changes in immune function after rituximab.