It has been suggested that liver allografts are less sensitive to lymphocytotoxic antibodies than other organ allografts. In this experimental study in sensitized inbred rat recipients, we have used extracorporeal liver hemoperfusion to study interactions between the liver and lymphocytotoxic antibodies. Donor-specific liver hemoperfusion can delay hyperacute rejection of heart allografts and reduce the level of lymphocytotoxic antibodies. Immunofluorescence examination of the hemoperfused liver revealed deposits of C3 on Kupffer cells and of IgG on sinusoidal cells. In control rats in which a third-party liver, a donor-specific splenic or renal hemoperfusion was performed, heart allograft survival was less prolonged. The decrease in antibody levels was not significant and the deposit of C3 and IgG was much less evident. Similarly, previous blockade of the Kupffer cells of the donor-specific hemoperfused liver by dextran sulfate suppressed the effect of liver hemoperfusion. These results support the hypothesis that resistance of the liver to hyperacute rejection might be due to a massive and nontoxic absorption of lymphocytotoxic antibodies onto nonparenchymal liver cells.