Thrombocytopenia developed in 23 patients with rheumatoid arthritis treated with gold salts over 25 years. All patients recovered, and there were no episodes of life-threatening hemorrhage; four patients eventually needed splenectomy. The clinical presentation of gold-induced thrombocytopenia and its treatment and outcome are reviewed. Because gold-induced thrombocytopenia is believed to have an immunologic basis, we sought an association between this complication and antigens of the human leukocyte antigen (HLA) region. The most significant finding was the association of the HLA-DR3 alloantigen in 12 of 15 of these patients compared with 26 of 84 in a control population (x2 12.9, p less than 0.001). This study provides further evidence that gold-induced thrombocytopenia is immunologically mediated and that genes of the major histocompatibility complex are involved.