We describe the clinical findings, laboratory and ancillary studies, and histopathologic findings of 2 patients with hepatitis C virus infection who developed inflammatory myopathy and interstitial lung disease. A review of pertinent literature revealed several other patients with a similar cluster of clinical manifestations. The inflammatory myopathy in the cases reported here was atypical and distinct from that found in the antisynthetase syndrome because it was characterized by mild or intermittent elevation of creatine phosphokinase, absence of anti-JO1 antibodies, and excellent response to oral corticosteroids. Thus, this report supports the hypothesis that hepatitis C virus infection may cause both inflammatory myopathy and pulmonary fibrosis. We suggest that evaluation for hepatitis C virus infection should be pursued in all patients with inflammatory myopathy and pulmonary fibrosis irrespective of anti-JO1 status. We further suggest that hepatitis C should be considered as another cause of myositis and interstitial lung disease in addition to the antisynthetase syndrome.