Ninety-two patients with active rheumatoid arthritis (RA) were entered in a randomized double blind study of 24 weeks comparing cyclosporine (initial daily dose 5 mg/kg) with D-penicillamine (initial daily dose 250 mg). The groups were well balanced in baseline characteristics. In the cyclosporine group, 10 patients stopped prematurely, one because of inefficacy. In the D-penicillamine group, 9 patients stopped prematurely, 3 because of inefficacy. The 2 antirheumatic drugs were equally effective in reducing disease activity, except for a significant (p = 0.005) decrease in erythrocyte sedimentation rate with D-penicillamine treatment. We conclude that under the conditions of this trial, cyclosporine can serve as an alternative to D-penicillamine for the treatment of patients with RA.