Pig tissues were screened by immunofluorescence with lectins, mAb, and human natural antibodies for the presence of carbohydrate antigens, which may be potential targets for hyperacute vascular rejection in pig to man xenotransplantation. The unfucosylated monomorph linear B-antigen was found at the surface of all porcine vascular endothelial cells. This pig linear-B antigen reacts strongly with the anti-aGal isolectin B4 from Griffonia simplicifolia 1 and with human natural anti-[alpha] Gal antibodies specifically purified by affinity chromatography on synthetic oligosaccharides containing the terminal nonreducing [alpha] Gall+/-3 [beta] Gal-R disaccharide. This antigenic activity is destroyed by treatment of pig tissues with [alpha]-galactosidase. The localization of this linear-B epitope on vascular endothelium and its reactivity with natural human anti-aGal antibodies suggest that it may play a major role in the hyperacute vascular rejection of pig to man organ xenografts. The lectin from Maackia amurensis reacting with [alpha] NeuAc2+/-3 [beta] Gall+/-4GlcNAc/Glc was also positive on pig vascular endothelium, but we do not know yet whether there are human natural antibodies reacting with the carbohydrate recognized by this lectin.