OBJECTIVE To compare the efficacy and tolerability of 4 immunosuppressants in treating Graves' ophthalmopathy (GO). METHODS Seventy-five untreated GO patients were enrolled in this study. The diagnosis of GO was based on the presence of the typical clinical features and exclusion of possible cranial/orbital diseases. In group A, 31 patients were randomly assigned to receive either prednisone (n = 16, treatment completed in 13 cases with doses of 40 mg, 20 mg and 10 mg per day for 4 weeks) or tripterygium wilfordii multiglycoside (TW, n = 15, 30 - 60 mg per day); in group B, 23 adults were randomized to receive cyclosporin A (CsA, n = 11, 5 - 6 mg per kilogram of body weight per day) or mycophenolate mofetil (MMF, n = 12, 16 - 18 mg per kilogram of body weight per day) therapy. The remaining 21 patients (control group) were given only anti-thyroid drugs and levo-thyroxine. The disease severity and therapeutic response were quantitatively assessed according to the Ophthalmopathy Index Scoring System from Given-Wilson (1989) with sensible modification. Improvement or progression of ophthalmopathy was defined if the difference, either increase or decrease, of the score, reached 3 or more in the ophthalmopathy index. If this did not occur, a lack of response was indicated. RESULTS After 12 weeks, 7 of the 13 treated with prednisone improved and the remaining 6 lacked response. In the TW group, 10 of the 15 responded to the therapy; 5 had no change. There was no significant difference in clinical response between the above 2 groups (P > 0.05). Five CsA-treated and 11 MMF-treated patients responded to the therapy (45% vs 92%; P < 0.05). It seems that MMF is more effective than CsA in the treatment of GO, although a significant decrease (P < 0.01) in the mean score of the CsA group has also been shown at the end of the course. Four of the controls improved, 5 (24%) showed worsening of ophthalmopathy, and the remaining 12 (57%) had no significant change. In the prednisone group, 3 gained body weight by more than 5%, and 2 developed impaired glucose tolerance. These two and one of the three weight gaining patients ceased the therapy. CONCLUSIONS New immunosuppressant MMF may be more effective than CsA in the treatment of Graves' ophthalmopathy. TW may be equally effective as and perhaps better tolerable than prednisone in the immunotherapy of Graves' ophthalmopathy.