Several clinical and experimental findings suggest that liver allografts are less sensitive than other organ allografts to lymphocytotoxic antibodies. In this experimental study in hypersensitized inbred rat recipients, rejection of liver allografts was delayed compared to that of heart allografts. Furthermore, there was a marked decrease in the level of cytotoxic antibodies after liver allografting but not after heart allografting in these animals. The decrease in the level of antibodies also occurred after donor-specific extracorporeal liver hemoperfusion in hypersensitized recipients. Whether the decrease was caused by a massive absorption of antibodies on the liver or related to excretion of major histocompatibility complex antigens in a soluble form remains to be demonstrated. These results support the hypothesis that the liver has a privileged position in regard to rejection and are consistent with clinical observations made following ABO incompatible or cross-match positive liver transplantations.