T cell subsets in 10 patients receiving amiodarone were evaluated, and their thyroid function and antithyroid antibodies were assessed. A generalized increase in a recently discovered subset of T cells expressing a complex ganglioside antigen reacting with monoclonal antibody 3G5 was found. Two patients, one with hyperthyroidism and the other with euthyroid Graves' ophthalmopathy, had an additional T cell abnormality--marked increase in Ia-positive T cells (an abnormality typical of patients with spontaneous Graves' disease). In the hyperthyroid patient, the Ia-positive T cells disappeared within three weeks after amiodarone was discontinued. The other patients receiving amiodarone had normal numbers of Ia-positive T cells. These studies indicate that amiodarone alters a major resting T cell subset for almost all patients and is associated with T cells expressing the Ia antigen in selected patients. These T cell abnormalities suggest that amiodarone precipitates organ-specific autoimmunity in susceptible persons.