Hepatic xenografts can tolerate hyperacute rejection owing to their lower susceptibility to humorally mediated injury. We investigated the possibility of long-duration xenoperfusion without immunologically controlling natural antibodies or complements. Pig livers were perfused for 9 h with human blood (Group 1) or pig blood (Group 2). Physiological conditioning and administration of prostaglandin E1 and insulin was characteristic of our system. The portal vein and hepatic artery pressure and bile production did not significantly differ between the two groups. Despite a gradual decrease throughout the perfusion, overall oxygen consumption was significantly higher in Group 1. Liver enzymes were released at higher levels in Group 1. Histological examination revealed intact hepatic architecture in Group 2, while in Group 1 interlobular morphology was severely damaged by endothelial disruption, although hepatic sinusoidal architecture was preserved. It is concluded that, despite biochemically and histologically confirmed tissue injury, graft viability was well-maintained in xenoperfusion even without immunological manipulations.