Objective. Rheumatoid arthritis (RA) is characterized by decreased expression of CD7 in the peripheral blood and in the synovium. The present study was designed to identify the basis for and functional consequences of this decreased expression. Methods. Peripheral blood lymphocytes from normal controls and from patients with RA or systemic lupus erythematosus (SLE), and T cell lines derived from rheumatoid synovium, were evaluated using 3-color fluorescence-activated cell sorter analysis. Results. Normal subjects and most SLE patients expressed homogeneous, bright CD7 on CD4+, CD45RA+ cells, whereas RA patients demonstrated a significantly increased proportion of CD7- cells. T cell lines derived from rheumatoid synovium demonstrated a striking deficiency of CD7 on CD4+, CD45RA- cells. CD4+, CD45RA+ cells from RA patients changed phenotype after in vitro activation to CD45RA negativity, with up-regulation of CD7. CD7-, CD4+, CD45RA- cells were assessed for their ability to induce pokeweed mitogen-driven IgM and IgM-rheumatoid factor synthesis, and they were found to be potent helper/inducer cells. An increased population of CD7-, CD4+ cells in peripheral blood was found to predict a low response to recall antigens. Conclusion. The low expression of CD7 in RA may explain some of the immune abnormalities which may contribute to the pathogenesis of this disease.