Combined therapy with systemic corticosteroids and orbital cobalt radiotherapy has been shown to be an effective treatment of severe Graves' ophthalmopathy. The potentially serious side-effects of large doses of systemic corticosteroids prompted us to evaluate the use of retrobulbar corticosteroids instead of systemic corticosteroids. Forty-four patients with active Graves' ophthalmopathy were given orbital cobalt irradiation (total dose 2000 rads) and retrobulbar methylprednisolone acetate (14 bilateral injections at 20-30 d intervals). The degree of ocular involvement and responses to treatment were evaluated by numerical scoring (ophthalmopathy index, OI) and clinical assessment. Excellent or good responses were observed in 11 out of 44 patients (25%), 24 (55%) showed slight responses, and no change was found in 9 patients (20%). The initial OI mean score was 5.9; the final score was 3.2, with a change of -2.7 (P less than 0.001). Regression or partial improvement was observed in most cases (35/44, 80%) with soft tissue changes, and in all 9 cases with sight loss due to optic neuropathy. Proptosis, corneal lesions and extra-ocular muscle involvement were less responsive, since regression or partial improvement was observed in 39% (12/31), 50% (8/16) and 31% (13/42), respectively. No major side-effects were observed. The effects of this type of therapy and those obtained by combined therapy with systemic corticosteroids and orbital radiotherapy were compared in two groups of 30 patients each, randomly assigned to either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)