Combination therapy in rheumatoid arthritis (RA) with 2 or more disease modifying antirheumatic drugs (DMARD) is theoretically attractive if the drugs exert additional or even synergistic effects and have different toxicity patterns to avoid cumulative toxicity. The combination of cyclosporin A (CsA) with chloroquine has shown in in vitro studies a synergistic ability to inhibit the proliferation of peripheral blood mononuclear cells and clonal T cells and the production of interferon gamma by clonal T cells. This synergy is probably based on different mechanisms of action of the 2 drugs: CsA primarily inhibits the production of interleukin 2 (IL-2) (and other cytokines) at the level of transcription, whereas chloroquine primarily inhibits the responsiveness of T cells to IL-2 stimulation. To evaluate whether these in vitro data can be extrapolated in vivo, a large 2 phase trial has been initiated in the Netherlands in which the combination of CsA with chloroquine is evaluated in patients with RA.