In immediately vascularized xenografts, the presence of species-specific preformed natural antibodies associated with the activation of the host complement system has been reported to induce hyperacute humoral rejection in discordant combinations. Furthermore, complement activation on the endothelial cells of xenografts has been suggested to play a major role in hyperacute rejection. On the other hand, in neovascularized xenografts, such as pancreatic islets of Langerhans, the absence of initial vascularization has been suggested to avert hyperacute humoral rejection and that the rejection might be cell mediated. Nevertheless, islet xenografting in higher mammals has been reported to result in an exceedingly brief period of graft functioning, which suggests that humoral immunity might play a significant role in islet demise. Thus, we hypothesized that, in islet xenotransplantation, islets might be hyperacutely rejected by antibody-dependent and/or antibody-independent activation of complement, not by cell-mediated mechanisms only. We have regarded humoral immunity, such as complement activation, as an important trigger of vascularized or neovascularized xenograft rejection. Based on this viewpoint, we have conducted various experiments on xenotransplantation of immediately vascularized organ or neovascularizing tissue, such as islets employing sulfonic polymer poly-(styrene sulfonic acid) (PSSa) carrying a strong anticomplementary effect in which we have originally focused on its chemical characteristics. PSSa (Toyo Soda Manufacturing Co, Tokyo, Japan) is a synthetic polymer that has a molecular weight of about 50,000 d (Fig 1), and is used clinically as an ion-exchange resin, sodium polystyrene sulfonate (Kayexalate, Torii Pharmaceutical Co, Tokyo), which is administered anally into patients' lower intestinal cavity.