Cyclosporin is a non-cytotoxic immunomodulating drug which inhibits NF-AT-dependent IL-2 transcription in lymphocytes. Cyclosporin is, therefore, beneficial as a monotherapy or as a combined therapy with methotrexate for refractory rheumatoid arthritis (RA). We also document that cyclosporin recovers the low concentration of intracellular multidrugs in lymphocytes by competitively binding to P-glycoprotein, a product of multidrug resistance gene-1, in vitro. Thus, cyclosporin could be used for the reversal of multidrug resistance, experienced in patients with longterm treated RA.