To predict interferon-alpha (IFN-alpha)-induced thyroid dysfunction, anti-thyroglobulin (anti-TgAb) and anti-thyroid peroxidase antibodies (anti-TPOAb) were determined by radio-immunoassay (RIA) before IFN-alpha treatment in 30 patients with chronic hepatitis C in whom the conventional haemagglutination test had failed to detect anti-thyroid auto-antibodies. Seven patients developed thyroid dysfunction during IFN-alpha treatment (transient thyrotoxicosis in four patients, transient hypothyroidism in two, and Graves' disease in one). Anti-TgAb and/or anti-TPOAb were detectable before IFN-alpha treatment in six of these seven patients, while these antibodies were detected before treatment in only four of 23 patients who did not develop any thyroid dysfunction. The prevalence of these antibodies was significantly higher (P = 0.002) in the former group of patients than in the latter. In four patients with detectable anti-TgAb before treatment but no subsequent thyroid dysfunction, the antibody disappeared during IFN-alpha treatment. Haemagglutination tests for anti-thyroid microsomal antibodies have previously been reported to be a useful predictive marker of IFN-alpha-induced thyroid dysfunction. In conclusion, sensitive detection of anti-thyroid auto-antibodies using RIA may also be useful for the prediction of IFN-alpha-induced thyroid dysfunction in patients with a negative haemagglutination test.