T cell depletion has been demonstrated to have therapeutic potential in patients with rheumatoid arthritis and several agents which deplete or inactivate T cells are currently being evaluated in clinical trials. We treated six patients with active rheumatoid arthritis with one such agent, the murine IgG1 anti-CD5 immunoconjugate CD5 Plus, as part of a multicenter trial. Measurement of in vitro synthesis of IgM and IgM-rheumatoid factor by peripheral blood mononuclear cells obtained from patients before, during, and after treatment, was performed using enzyme-linked immunoassays. Subsets of T and B lymphocytes were measured by flow cytometry. Significant T cell depletion was observed on Days 2 and 5 during the treatment period and was associated with increased in vitro rheumatoid factor (RF) production on Days 5 and 8 in 4 of the 5 patients with significant pretreatment levels of RF synthesis. No apparent relationship to serum RF levels or clinical responses was noted. These results implicate a role for T cells in the control of IgM-RF production in patients with rheumatoid arthritis.