The records of 155 consecutive patients who underwent successful heart transplantation (HTx) were reviewed to document the incidence of hepatitis C (HCV) infection. One patient was HCV RNA positive pre-HTx, and 12 patients (8%) developed transient or permanent HCV positivity post-HTx. HCV RNA positivity was associated with biochemical features of liver injury. Liver biopsy was performed in 8, and demonstrated features of chronic hepatitis in all. Two patients died of chronic liver failure at 50 and 56 months post-HTx, respectively. Interferon therapy was given to three patients, two of whom converted to HCV negativity. This study suggests that HCV infection is more common than previously anticipated in HTx patients, and varies from a mild transient condition to a fatal chronic liver failure.