In this study, we evaluated whether hepatic steatosis affects the viral response to interferon (IFN) and ribavirin combination therapy in Japanese patients with chronic hepatitis C (CHC). Eighty CHC patients treated with IFN alpha-2b and ribavirin for 24 weeks were evaluated retrospectively. Liver biopsy specimens were assessed histopathologically, and grade of steatosis was scored as follows: grade 0: <5%; grade 1: 5-33%; grade 2: 33-66%; grade 3: >66%. Sustained viral response (SVR) was defined as negative for HCV-RNA by high-sensitivity qualitative reverse transcription-polymerase chain reaction (RT-PCR) at 24 weeks post-treatment. Hepatic steatosis graded 2 and higher was seen in 28.8% patients, whose average BMI were significantly higher than those in grade 0 patients. Grade of steatosis was well correlated with elevation in serum aminotransferases and gamma-glutamyltranspeptidase (gamma-GTP) levels, but not with histological degree of inflammation and fibrosis. The SVR rates were significantly lower in the group with overt steatosis (grade 2/3) as compared to the group with less steatosis (grade 0/1), the values being 30.4% and 57.9%, respectively. Moreover, grade of steatosis was selected as an independent negative factor for SVR in multivariate analysis. In conclusion, hepatic steatosis is an important predictor of poor response to therapy of IFNalpha-2b and ribavirin in patients with CHC.