In untreated hepatitis virus (HCV)-positive renal transplant patients, the rate of liver fibrosis progression is low. In contrast, in those treated by ribavirin monotherapy, liver fibrosis score increased significantly after only 1 year of ribavirin monotherapy. The aim of this study was to identify the factors that might contribute to accelerate liver fibrosis progression in this population. Eleven patients were included in the study. Intrahepatic transforming growth factor (TGF)-beta, interferon (IFN)-gamma, and interleukin (IL)-10 mRNA quantification determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) were similar before and after ribavirin therapy. The number of amino acid substitutions observed in the hypervariable region (HVR)-1 of the HCV genome between baseline and 1 year after ribavirin monotherapy was low, i.e., 3 (1-11) amino acid substitutions, suggesting the absence of a high selection pressure induced by ribavirin. In contrast, due to ribavirin-induced hemolysis, there was a significant increase in serum ferritin levels (P = 0.02) and in intrahepatic iron deposition (P = 0.04). Transferrin level and total iron-binding capacity decreased significantly during ribavirin monotherapy (P = 0.004). The increased liver fibrosis observed in renal transplant patients receiving ribavirin monotherapy could be related to ribavirin-induced anemia. Severe chronic hemolysis is responsible for iron overload, liver iron deposition, and an acceleration in the progression of liver fibrosis.