The effect of alcohol intake on the efficacy of interferon (IFN) therapy was evaluated retrospectively in patients with chronic hepatitis C diagnosed by liver histology and positive serum hepatitis C virus (HCV)-RNA. Patients included 119 given IFN therapy and 11 no IFN therapy. Serum HCV-RNA was measured 6 months after discontinuation of IFN therapy in 92 treated patients, 27.2% of whom showed disappearance of serum HCV-RNA. Multivariate logistic regression analysis revealed that this disappearance was affected by alcohol intake, the presence of its history (p < 0.05) or cumulative alcohol consumption (kg) (p < 0.01), and serum HCV-RNA levels (p < 0.001). The odds ratio associated with serum HCV-RNA still positive at 6 months was 7.016 (95% confidence interval: 1.444-34.082) and 1.004 (1.001-1.007) for the presence of alcohol intake history and the cumulative alcohol consumption, respectively. Other predictor variables–such as sex and age of patients, history of blood transfusion, HCV genotype, histological findings of the liver, and types of IFN– had no influence on the efficacy of the therapy. Cumulative alcohol consumption showed a negative correlation with serum HCV-RNA levels pretreatment, when the outcome variable was divided into two categories based on serum HCV-RNA levels: 106 copy/ml or less and 107 copy/ml or more. Alcohol intake was positively correlated with histological extent of alcoholic fibrosis, but affected neither grading nor staging of chronic viral hepatitis. We conclude that alcohol intake was a risk factor on the efficacy of IFN therapy in chronic hepatitis C patients. This effect was independent of serum HCV-RNA levels and histological findings specific for viral hepatitis in the liver.