Irreversible nephrotoxicity has limited the use of cyclosporine in rheumatoid arthritis (RA). In a randomized clinical trial we compared 26 weeks of cyclosporine (5 mg/kg) and D-penicillamine (250 mg) treatment in 92 patients with RA with a serum creatinine less than 100 mumol/l. We adjusted the starting dose according to clinical response and side effects. During cyclosporine treatment the serum creatinine increased by median 15% (p less than 0.0001 vs baseline), quickly reversible after stopping (median followup: 1.6 years). Six patients stopped cyclosporine prematurely because of nephrotoxicity. In the D-penicillamine group the values remained at baseline.