Immunoglobulins (IgG, IgA, IgM) have been measured by radial immunodiffusion method in 43 patients affected with rheumatoid arthritis and treated with d-penicillamine (Pen). Erythrocyte sedimentation rate (ESR), serum alpha 2 and gamma globulins have alos been determined. Serum samples were collected before therapy and after 3 months (43 cases), 6 months (30 cases), 9 months (20 cases), and 12 months (15 cases, respectively). Pen was administered starting from 150 mg/day up to 600-750 mg/day. IgG did not show any significant change, whereas IgA significantly decreased only at 6 month and IgM at every follow-up. During therapy, a decrease in ESR was observed in all determinations, while alpha 2 and gamma globulins showed a reduction at 9 and 12 month follow-up. In rheumatoid arthritis Pen seems to reduce IgM and partially IgA, along with some inflammatory indices. Thus, an inhibitory effect of Pen on immunological reactions is suggested, although a direct breakdown activity on immunoglobulins cannot be excluded.