OBJECTIVE To evaluate the effects of long term treatment of rheumatoid arthritis (RA) with high doses of intravenous immunoglobulins (IVIg). METHODS Ten patients with active RA and prior unsuccessful treatment with at least one slow acting antirheumatic drug were treated with 400 mg/kg of IVIg for the first three days and then once a month for 12 months. Clinical evaluation and laboratory analysis were performed every month. Serum levels of tumour necrosis factor alpha (TNF alpha), soluble interleukin-2 receptor (sIL-2R), IL-1 alpha, IL-1 beta, IL-6 and interferon gamma (IFN gamma) were measured at baseline and at three monthly intervals for 15 months. RESULTS Although laboratory parameters were not influenced by the treatment, a late but significant clinical improvement was observed after six months. Serial measurement of cytokines revealed a rapid and persistent decrease in serum TNF alpha and a late and significant reduction in sIL-2R concentrations. CONCLUSIONS This study suggests that IVIg can ameliorate the symptoms and improve the functional capability of RA patients. This effect is associated with a partial modulation of serum concentrations of inflammatory cytokines and, more interestingly, with a late decrease in sIL-2R which correlated with the late reduction in disease activity.