Combination of pegylated interferon and ribavirin has been the standard program for hepatitis C virus (HCV) infection. Pulmonary complications, although uncommon, have been reported in association with the use of interferon, and pleural effusion is rare. We report the second case of pleural effusion and interstitial pneumonitis in a patient treated with pegylated interferon and ribavirin for chronic HCV infection. The respiratory symptoms of our patient continued to progress even though the treatment with pegylated interferon had been withdrawn, but the symptoms improved dramatically following treatment with steroids.