The hepatitis-C virus has been the most prevalent cause of chronic hepatitis in both blood and organ recipients. The introduction of a second-generation immunoassay for antibodies to the hepatitis-C virus (HCV 2.0) provided the opportunity to determine if the hepatitis-C virus can be transmitted through tissue transplantation. Banked sera from tissue donors that had previously been found to be non-reactive to the first-generation hepatitis-C virus antibody assay (HCV 1.0) and non-reactive for antibodies to hepatitis-B core antigen were retested with HCV 2.0. The sera from two donors were reactive; the transplant records of recipients of tissues from these donors were reviewed, and the surgeons or hospitals were contacted. The tissue recipients were tested with HCV 2.0, and positive sera were tested for hepatitis-C virus RNA by polymerase chain reaction. Viral nucleic acids isolated from viremic donors and recipients were analyzed for identity by sequencing of the hepatitis-C virus envelope gene (E2) hypervariable region. There were twenty-one grafts, which had been treated with gamma radiation, from one donor; thirteen had been transplanted to twelve recipients. Serum samples from six of the recipients were tested; one was reactive. This patient had other risk factors for infection with the hepatitis-C virus, and sequence analysis demonstrated non-identity between the donor and recipient hepatitis-C virus isolates. Nine of twelve grafts from a second donor had been transplanted in nine recipients. Serum samples from five patients were tested with HCV 2.0; four were reactive. In three of the four patients, the sera were determined to be positive for the hepatitis-C virus by polymerase chain reaction. E2 sequence analyses of hepatitis-C virus RNA isolates from two of these recipients demonstrated sequence identity with the donor isolate. The results of the present report demonstrate that the hepatitis-C virus can be transmitted by bone, ligament, and tendon allografts. They also support the need for testing of all tissue donors for antibodies to the hepatitis-C virus before the tissue is released for transplantation. The results also suggest that seventeen kilo-gray of gamma radiation may inactivate the hepatitis-C virus in tissue.