Objective. Recent data suggest that the reconstituting peripheral B cell compartment after B cell depletion therapy may be functionally immature, with a preponderance of transitional B cells and a paucity of memory B cells. This study was undertaken to determine the magnitude, duration, and cause of these defects in rituximab-treated systemic lupus erythematosus (SLE) patients.Methods. Fifteen patients with SLE previously treated with rituximab as part of a phase I/II doseescalation study were evaluated during a long-term followup (mean followup period 41 months). B cells from peripheral blood and tonsils were assessed using multicolor flow cytometry, and their developmental pathway was classified based on the expression of defined surface markers. Rituximab is a chimeric mouse/human monoclonal antibody directed against the B cell-specific antigen CD20, which depletes B lymphocytes in vivo from the pre-B cell stage in bone marrow, when CD20 is first expressed, to the mature B cell stage. Due to its efficacy in the depletion of both normal and malignant B cells, rituximab represents an effective treatment for B cell lymphomas and has emerged as a promising treatment for multiple autoimmune diseases, including systemic lupus erythematosus (SLE), as we and other investigators have previously described (1-4).However, the long-term immunologic effects of rituximab, the mechanism(s) whereby B cell depletion Dr.