The severe shortage of human organs and tissues constitutes one of the major factors still limiting the widespread clinical use of pancreatic islet transplantation for many patients with insulin-dependent diabetes mellitus. The use of xenogenic islets could solve the problem of donor shortage. The pig appears to be the most likely donor species for xenotransplantation into humans for a variety of reasons.In organ xenotransplantation, one of the major obstacles is hyperacute rejection. The binding of human preformed natural antibodies (PNAbs) to the pig cells and subsequent activation of complement are considered the prime movers in this process. A carbohydrate terminal sugar, Galα(1-3) Gal, on pig endothelial cells is believed to be a major target for human PNAbs. It is not well known whether human PNAbs will also play a role in the rejection process in pig-to-human islet transplantation. The aim of the present study was to assess the expression of Galα(1-3)Gal epitopes on pig islets and the presence of PNAbs in human sera directed against pig islets.