Forty patients with active rheumatoid arthritis were included in this monocentre double-blind study comparing the therapeutic efficacy and safety of the immunomodulator OM-8980 with that of D-penicillamine. After 12 months of treatment, the parameters of Ritchie index, duration of morning stiffness, pain assessed by a visual analogue scale and categories, number of swollen joints, grip strength and erythrocyte sedimentation rate (ESR) were all significantly improved with OM-8980, as was the case for the Ritchie index, number of swollen joints and ESR with D-penicillamine. Significant intergroup differences were recorded for pain categories in favour of OM-8980 and for the Ritchie index and number of swollen joints in favour of D-penicillamine. The need for concomitant anti-inflammatory therapies and the assessment of efficacy by physicians and patients did not differ significantly between the two groups. OM-8980 was significantly better tolerated than D-penicillamine (5 patients with 5 side effects as compared with 12 patients with 16 side effects). OM-8980 can thus be regarded as an efficient and well-tolerated slow-acting drug for the treatment of rheumatoid arthritis.