To assess therapeutic effect and toxicity of D-penicillamine in relation to HLA antigens, 111 consecutive patients with rheumatoid arthritis (RA) were followed for a period of 7-9 years. Side effects occurred in 60% and were the main reason for withdrawal in 52%. HLA typing was performed in 86; overall frequencies were comparable with those found in other studies in patients with RA. Drug induced proteinuria (5 patients) was associated with HLA-B8/DR3 (60 vs 9%), and thrombocytopenia (23 patients) with HLA-DR4 (94 vs 67%). Therapeutic effect was good in 26 (23%), and moderate in 30 (27%). No single variable, including HLA antigens, was predictive of effectiveness. It is concluded that although some of the side effects were associated with HLA antigens, HLA typing is not useful in predicting the outcome of treatment with D-penicillamine.