The prevalence of thyroid autoimmunity is high in patients with chronic idiopathic urticaria (CIU), but in few selected patients the possible clinical benefit of levothyroxine sodium or antithyroid drugs has been studied. The objective of the present study was to confirm the prevalence of antithyroid antibodies in patients with CIU and to investigate the clinical response to levothyroxine sodium or methimazole. Antithyroglobulin and antiperoxidase antibodies were measured in 170 consecutive patients with CIU. Twenty-five (14.7%) had an antithyroglobulin or antiperoxidase antibody levels > 180 lU/ml and all but three were women. Twenty patients with CIU and thyroid autoimmunity were treated with levothyroxine sodium if hypothyroidism or normal thyroid function were present (18 patients) and with methimazole if hyperthyroidism was detected (two patients). Clinical response was evaluated by a clinical score. Autologous serum skin test before treatment was performed in 18 patients with thyroid autoantibodies. Urticaria resolved rapidly in two patients with Graves' disease. The clinical response of urticaria to levothyroxine sodium treatment was good in 15 patients and partial in two, whereas only one patient showed no improvement in clinical score (p < 0.0005). No changes in the antithyroglobulin or antiperoxidase levels were detected. Five patients reported adverse effects. The autologous serum skin test was positive in 10 patients and negative in eight. After successful treatment the test was repeated in six patients, proving negative in four and significantly diminished in two. We concluded that patients with CIU and thyroid autoimmunity benefit from treatment with levothyroxine sodium or antithyroid drugs. Antithyroid antibodies and positive autologous serum skin test in these patients could be markers of autoimmune disease with several target organs.