A discrepancy between E-rosette-forming cells and total T cells identified by monoclonal antibodies (Leu-1+) was observed in patients with systemic lupus erythematosus (SLE). E-Rosette-forming cell percentages of peripheral blood mononuclear cells (MNC) were significantly lower than those observed in normal individuals, in contrast to the percentage of Leu-1+ cells in SLE patients which were not different from those of normal values. The cells which did not form E rosettes, but stained positively with the monoclonal anti-Leu-1 antibody (E-, Leu-1+) had certain functional capability evidenced by their ability to amount a proliferative response to T-cell mitogens, phytohemagglutinin and concanavalin A, but failed to provide T-helper-cell activity to support the differentiation of normal B lymphocytes into immunoglobulin-secreting cells following stimulation with pokeweed mitogen. Inhibition of E-rosette formation, but not of the staining for Leu-1, was demonstrated by incubating sera from SLE patients with normal MNC. These studies suggest that the T-cell markers, E+ and Leu-1+, do not necessarily characterize identical subpopulations of T cells. When referring to E- cells in studies with MNC from SLE patients, it should be realized that this population includes, in addition to B cells and macrophages, cells staining positively for Leu-1 antigen and reactive to T-cell mitogens.