Hyperthyroid Graves' disease (GD) is a B-cell-mediated disease caused by antibodies stimulating the thyroid stimulating hormone (TSH) receptor (TRAb). A proportion of patients (40-60%) present with an associated ophthalmopathy (TAO), a progressive inflammatory autoimmune disease of the retroorbital tissue. We thought that the anti-CD20 monoclonal antibody rituximab (RTX), by inducing transient B-cell depletion, may potentially modify the active inflammatory phase of TAO. One patient with GD and TAO in its active phase and unresponsive to steroid, was treated with RTX. Whereas the ophthalmopathy responded to RTX therapy and a decrease in the clinical activity score from 5 to 2 was observed during the B-cell depletion, serum antithyroid antibodies, and in particular serum TRAb, were not affected by therapy. When the patient underwent total thyroidectomy, we found B-cells in the thyroid tissue specimens. The eye disease remained stable (clinical activity score=2) and the patient subsequently underwent orbital decompression to correct proptosis of the eye. At that time we did not find lymphocytes in any of the orbital tissue specimens. We believe that RTX therapy in GD may cause amelioration of ophthalmopathy by depleting total lymphocyte population in the orbit, but not lymphocyte depletion in thyroid tissue with consequent unchanged serum TRAb levels.