A 39-year-old man with chronic hepatitis C was administered interferon beta (3 MU twice a day) daily. Before interferon therapy, he did not have any symptoms and abnormal data related with autoimmune diseases. On the 16th day of interferon, mono-arthritis occurred at his right elbow. Anti-nuclear antigen or rheumatoid factor was still negative. Discontinuation of interferon for a week with non-steroid anti-inflammatory drug relieved his symptom. Re-administration of interferon (6 MU once a day, three times a week) did not induce arthralgia any more. Administration of interferon beta twice a day may accelerate the cellular immunity twice. Careful observation should be taken even in the cases without pre-existing autoimmune diseases.