Liver allografts have a privileged status in regard to acute rejection. In this experimental study, we have analyzed the immunosuppressive effects of an extracorporeal liver hemoperfusion. In the LEW-to-BN combination of inbred rats, donor-specific liver hemoperfusion can significantly delay acute rejection of heart allografts. Analysis of the immunological status of these animals revealed a significant decrease in donor-specific lymphocytotoxic antibodies and in cytotoxic T lympholysis. Reactivity in mixed lymphocyte culture was normal. After third-party (DA) liver hemoperfusion or after donor-specific (LEW) splenic hemoperfusion, prolongation of heart allograft survival was moderate. Previous blockade of Kupffer cells suppressed the effects of donor-specific liver hemoperfusion. These results suggest that the sequestration by Kupffer cells of a clone of cytotoxic T cells and/or lymphocytotoxic antibodies may explain the immunosuppressive effects of donor-specific liver hemoperfusion.