Patients with severe Graves' ophthalmopathy may or may not improve with systemic corticosteroids. In an attempt to find immunologic distinctions to correspond with this clinical phenomenon, we have evaluated various parameters in corticosteroid-responsive and corticosteroid-resistant individuals. Percentages and absolute numbers of thymus-derived active and total rosette-forming cells (A-RFC and T-RFC) underwent statistically significant (p < 0.001) increases during successful prednisone therapy in 17 patients . B lymphocytes and complement receptor mononuclear cells did not significantly change with steroid therapy. In the second group, five patients therapeutically resistant to corticosteroids presented with elevated A-RFC and normal T-RFC. When treated with oral prednisone, these patients' A-RFC decreased (p < 0.001), and the T-RFC were unchanged. Corticosteroids increased the lymphoblast transformation response to phytohemagglutinin (PHA) of a steroid-responsive patient, whereas steroids decreased the PHA lymphoblast transformation response of a corticosteroid-resistant patient. A disease activity index to correlate the clinical and immunologic data has been devised. The findings may allow the clinician to predict which patients with Graves' ophthalmopathy are likely to benefit corticosteroid therapy and which patients may be managed better by other methods.