Thyroid disease is a common side-effect of interferon-based antiviral therapy for chronic hepatitis C, which may lead to dose reduction or discontinuation of therapy. The aim of this study was to investigate changes in ultrasound morphology, thyroid function, autoimmunity as well as predictive factors for the development of thyroid dysfunction in patients with hepatitis C virus infection treated with pegylated interferon-alpha (PEG-IFN-alpha) and ribavirin. A total of 59 patients with chronic hepatitis C assigned for antiviral treatment with PEG-IFN-alpha and ribavirin were enrolled into the study. All patients were subjected to an ultrasound examination of the thyroid gland before treatment, and after 1, 3 and 6 months of antiviral therapy. In addition, thyroid function and autoimmune status were determined at fixed time-points. Prior and during the course of therapy, 11 patients (19%) developed thyroid dysfunction (one hypothyroidism, nine hyperthyroidism, one hyperthyroidism followed by hypothyroidism). Hyperthyroidism was shown to be Graves' disease in one patient and destructive thyroiditis in nine patients. Power-Doppler ultrasound could differentiate between destructive thyroiditis and Graves' disease. A reduction in echogenicity suggestive for a destructive process of the thyroid gland was observed even before changes in thyroid function of antibody status could be measured. Risk factors for the development of thyroid dysfunction were age, female gender, pre-treatment thyroid volume, pre-existing thyroglobulin/thyroid peroxidase antibodies and viral load. Changes in thyroid function are a common side-effect occurring during antiviral therapy with PEG-IFN-alpha and ribavirin. Ultrasound presents a simple complementary tool for screening and follow-up during antiviral therapy, which helps to differentiate between the common types of hyperthyroidism and gives insight into morphological changes of the thyroid gland during antiviral therapy.