Liver allografts have a privileged status with regard to hyperacute rejection. In this experimental study, we have used extracorporeal liver hemoperfusion in sensitized rats in order to analyze reactions between lymphocytotoxic antibodies and the liver. In sensitized BN rats, a donor-specific (Lewis) extracorporeal liver hemoperfusion can delay hyperacute rejection of heart allografts and reduce the level of lymphocytotoxic antibodies. The decrease in the level of antibodies could be due to massive absorption of antibodies by the liver or to release of major histocompatibility complex antigens in a soluble form. Immunofluorescent examination of the hemoperfused liver revealed important deposits of C3 on Kupffer cells and of IgG on sinusoidal cells. On the contrary, in control rats in which a third-party (DA) liver hemoperfusion was performed, heart allograft survival was less prolonged, the decrease in the level of lymphocytotoxic antibodies was not significant, and the deposits of IgG and C3 were much less evident. The level of circulating immune complexes was unchanged after a donor-specific or a third-party 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 on nonparenchymal liver cells.