BACKGROUND AND OBJECTIVE: It has been well documented that treatment of chronic hepatitis B and C infection with interferon alpha (IFN-alpha) can lead to the induction of thyroid autoantibodies and hypothyroidism. Thyrotoxicosis, however, is less frequently observed and less well characterized. PATIENTS AND METHODS: We reviewed the medical records of patients who developed thyrotoxicosis while receiving IFN-alpha for either chronic hepatitis B or C infection at Westmead Hospital between 1996 and March 2001. RESULTS: Ten patients (four males and six females) were found to have biochemical thyrotoxicosis. The patients could be divided into two groups with different characteristics. The first group consisted of six patients who had clinical manifestations consistent with Graves' disease, with either diffuse uptake in thyroid scintigraphy and/or positive thyroid-stimulating antibodies. They all required prolonged treatment with antithyroid medications. The second group included three patients who had transient thyrotoxicosis, with progression to hypothyroidism after resolution of thyrotoxicosis. CONCLUSION: Our study suggests that IFN therapy may provoke two different forms of thyrotoxicosis: a Graves' disease picture or a biphasic thyroiditis pattern. The two entities should be differentiated, as they have different implications for treatment.