OBJECTIVE To clarify the effect of hepatitis G virus (HGV) infection on chronic hepatitis C. METHODS Retrospective study. METHODS University hospital in Matsumoto, Japan. METHODS 189 randomly selected patients with histologically proven chronic hepatitis C, including 101 patients receiving interferon-alpha. METHODS Serum levels of HGV RNA were measured by reverse-transcription polymerase chain reaction. Clinical features, including liver histologic findings, hepatitis C virus (HCV) markers, and response of HCV to interferon-alpha were compared between HGV RNA-positive and HGV RNA-negative patients. RESULTS 21 of 189 (11%) patients with chronic hepatitis C were positive for HGV RNA. On average, patients with HGV RNA were younger than those without HGV RNA (mean age +/- SD, 46.6 +/- 13.0 years and 51.7 +/- 10.7 years, respectively); other demographic and clinical features were similar. The HCV genotype and HCV RNA level were distributed similarly between patients with and those without HGV infection. Ten of 101 patients with chronic hepatitis C who received interferon-alpha were positive for HGV RNA. The rate of sustained HCV response to interferon-alpha in patients with HGV infection (30%) was similar to that in patients without HGV infection (36%). The HGV RNA level decreased during therapy in all 9 patients in whom this value was measured. However, only 2 of these patients had a sustained HGV response after discontinuation of therapy. CONCLUSIONS Patients who only had HCV infection did not differ from patients with HCV and HGV co-infection in clinical presentation, HCV RNA level, or response of HCV to interferon-alpha therapy. Thus, HGV infection had no apparent influence on the clinical or virologic course of HCV infection. Hepatitis G virus was uniformly sensitive to interferon-alpha therapy, but only a few patients had a sustained virologic response.