Carriage of the epsilon4 allelic variant of the apolipoprotein E (ApoE) gene might affect the outcome of hepatitis C virus (HCV) infection. The liver transplantation setting offers the opportunity to verify the role of the donor's vs recipient's ApoE polymorphism. Twenty-four patients (16 men) with recurrent hepatitis C, all infected by HCV-1b and treated with interferon and ribavirin, were genotyped for ApoE variants. Liver biopsies were done at baseline and 12 months later After treatment, staging scores improved in 10 of 24 patients. Staging improvement was associated with recipient sex, completion of the full antiviral schedule, and recipient's epsilon4 carriage. The beneficial effect of epsilon4 carriage toward the progression of fibrosis was due entirely to the contribution given by male patients and was independent of the viral response. Recipients', but not donors', carriage of at least 1 epsilon4 allele might be associated with a better histologic outcome in recurrent HCV infection.