Thirty-one patients with seropositive rheumatoid arthritis treated with cyclosporin A (CsA) were evaluated for immune function prior to, during, and after 1 year of therapy. Patients whose pretreatment peripheral blood mononuclear cells were hypoproliferative in vitro to soluble recall antigens responded better clinically to CsA treatment than did the other patients. During therapy, proliferative responses became normal and remained so until 1-2 months after CsA was discontinued. At that time, the lymphocyte proliferation defect reappeared. In addition, patients who responded clinically to CsA had a higher percentage of Leu-7+ natural killer cells in their peripheral blood prior to therapy. All patients exhibited greater frequencies of cells that expressed interleukin-2 receptors, which decreased with CsA treatment. The clinical response to CsA appears to be associated with distinct immunologic parameters in rheumatoid arthritis.