OBJECTIVE: To report an instance of Hashimoto encephalopathy probably resulting from pegylated interferon alfa-2b and ribavirin. CASE SUMMARY: A 36-year-old woman with a 10-year history of autoimmune thyroiditis presented with symptoms and signs consistent with Hashimoto encephalopathy during therapy with pegylated interferon alfa-2b and ribavirin for chronic hepatitis C. DISCUSSION: Hashimoto encephalopathy is a rare autoimmune condition that occurs in patients with Hashimoto thyroiditis and high titers of antithyroid antibodies. It is characterized by a variety of nonspecific neuropsychiatric symptoms, increased cerebrospinal fluid protein level, and abnormal brain imaging and electroencephalogram. Prompt response to corticosteroids is observed in most cases. As of August 29, 2005, this is the first report of such an association. An objective causality assessment revealed that the Hashimoto encephalopathy was probably caused by the patient's medications. CONCLUSIONS: Hashimoto encephalopathy may rarely be triggered by interferon alfa therapy in susceptible patients.