SUMMARY. Liver steatosis is highly prevalent in chronic hepatitis C virus (HCV) infection, especially in patients infected with genotype 3 virus, but its significance for the outcome of antiviral treatment is not fully understood. We have monitored steatosis in liver biopsies from 231 patients with chronic HCV infection who received pegylated recombinant interferon-alpha and ribavirin in a phase III study (DITTO trial). The degree of steatosis, along with relevant metabolic parameters, was correlated with the early disappearance of virus and with the final outcome of treatment. Our data suggest that the presence of steatosis impairs the early reduction of viral load during treatment in patients infected with HCV genotype 3 and non-3. Steatosis negatively affected the final outcome of treatment mainly in patients infected with HCV genotype non-3 virus. Based on these findings, we propose that interventions aiming at reducing hepatic steatosis prior to the onset of antiviral therapy may be of benefit to patients infected with HCV of the non-3 genotypes. Patients infected with genotype 3, on the other hand, should be offered early antiviral treatment.