Thirty liver transplant recipients with recurrent chronic hepatitis C were randomly assigned to receive 24 weeks of therapy with subcutaneous injection of interferon alfa 3 million u thrice weekly or oral ribavirin 1.2 mg daily, 6 months after transplantation. The study was completed in 28 (93%) patients; 2 patients in the ribavirin group were withdrawn due to severe hemolysis. Normalization of serum aminotransferases occurred in 93% of ribavirin and 43% of the interferon patients. Although lobular inflammation was reduced in 64% of ribavirin patients and 21% of interferon patients, total histologic score did not improve significantly in either group. Post-treatment viremia was significantly reduced in the interferon patients, with undetectable HCV RNA in 46% at the end of the study compared to 17% in the ribavirin patients. In ribavirin patients, hemolysis (hemoglobin <10 g) occurred in 50% and a decrease in total leucocyte and lymphocyte counts was noted. In patients with recurrent HCV after liver transplantation, interferon retains an antiviral effect, but ribavirin was superior in normalizing serum aminotransferases and reducing lobular inflammation. These findings may provide a rationale for combination therapy in these patients if careful monitoring of hemolysis in ribavirin patients is carried out.