A 70-year-old Japanese woman with hepatitis C virus (HCV) infection was diagnosed with polymyositis and treated with high-dose prednisolone (PSL). The serum alanine aminotransferase (ALT) level increased from 78 to 345 U/l 1 week after initiating treatment, although the polymyositis settled promptly. Furthermore, the serum HCV RNA level increased markedly from 110 to 850 kIU/ml 3 weeks after starting treatment. Previously, the patient had suffered an occlusion of the left branch of the retinal vein secondary to hyperviscosity syndrome resulting from Sjögren's syndrome and low-dose PSL treatment had been commenced. The serum HCV RNA and transaminase levels had not increased during this low-dose PSL treatment. Although intensive immunosuppression is necessary as an initial treatment of several collagen diseases including polymyositis, high-dose PSL therapy may markedly augment the serum HCV RNA level and therefore careful observation is necessary in HCV-infected patients.