We are presently undergoing a hidden epidemic of hepatitis C infection in this country. While many individuals may have very slowly progressive courses with good health for decades, some develop cirrhosis relatively earlier in their disease process. These individuals are increasingly becoming candidates for liver transplantation, although the number of available livers is far less than the number of people with end-stage hepatitis C infection who might use one. Hepatitis C can recur in the new liver, but often does not become a serious problem. Instead, chronic rejection turns out to more often limit the longevity of the transplant. Chronic rejection of any solid organ entails cellular injury to endothelial cells, resulting in intimal proliferation, fibrosis, and eventually, ischemic injury to the graft. Immunosuppressive therapy is directed at controlling lymphocyte activity and minimizing cellular rejection. Autoantibodies are not involved in organ transplant rejection. The antibodies produced are alloantibodies directed only to the graft, but not to the host. Complement proteins are involved in the humoral component of acute rejection, and complement binding to alloantibodies increases graft damage. Complement protein production, however, is not affected by immunosuppressive therapy. HLA antigen expression is central to recognition of foreign cells in grafted tissue. HLA antigens are expressed constitutively by all normal cells, and immunosuppression does not affect their production.