Hepatitis B virus infection is one of the major causes of chronic liver diseases. Antiviral agents such as interferon alpha used to prevent the hepatic destruction. The mechanism of neuropsychiatric side effects due to interferon treatment is not well known. Although it is suggested in some studies that the psychiatric side effects of interferon decrease and stop after the cessation of the treatment, some others suggest that they may continue. A case of major depression due to interferon treatment for hepatitis B is presented here for the sake of the unusual time of occurrence and course of symptomatology.