Spontaneous autoimmune thyroid disease (SATD) shows familial aggregation. Some patients receiving amiodarone treatment have been found to develop thyroid dysfunction. Previously, we reported genetic predisposition among this group of patients, now we inform a prospective study which includes the search for autoantibodies and family history to identify risk factors in amiodarone treated patients, 40 of them with amiodarone related thyroid disfunction, and 100 without it; for comparison, 30 patients with SATD and a control group of healthy subjects were also studied. We looked for the presence of autoantibodies against thyroglobulin, smooth muscle, gastric mucosa, myocardium, mitochondria, epithelial intercellular substance, and basal membrane as well as antinuclear antibodies and rheumatoid factors; in addition the history of thyroid disease in first degree relatives was investigated. Organ-specific antibodies anti-thyroglobulin, gastric mucosa and myocardium were found with increased frequency in the three groups of patients compared with controls (p less than 0.05). The frequency of antihydroglobulin antibodies was similar in patients receiving amiodarone with or without thyroid dysfunction. Prognostic stratification revealed that this finding is independent of sex, age, dosage or duration of treatment. A family history of thyroid dysfunction was found more frequently among patients with SATD and amiodarone related dysthyroidism in comparison with patients receiving amiodarone without altered thyroid function (p less than 0.005). The appearance of clinical thyroid disease depends on individual genetical predisposition. In patients with a positive family history, the risk of developing clinical, thyroid disease is 7.6 when treated with amiodarone.