The vascular endothelium of all mammals tested to date expresses the αGal epitope, which is a major target for human natural antibodies. Birds, including the ratites (e.g., ostrich and emu) that might prove suitable as donors of hearts for humans, do not express αGal epitopes. Human anti-emu heart vascular endothelial antibodies were demonstrated not to be anti-αGal antibodies. The ratite heart is four-chambered and has many structural similarities to that of humans and other mammals. However, ratite vascular endothelium expresses βGal epitopes, and human plasma was demonstrated to be cytotoxic to both ostrich and emu aortic endothelial cells in culture. In vivo or ex vivo hemoperfusion of emu and ostrich hearts by baboon blood resulted in poor function of both hearts for <1 hour, with histopathologic features of hyperacute rejection seen in the ostrich, but not the emu, heart. We conclude that, despite the absence of αGal epitopes, the ratite offers no advantage over the pig as a donor of organs for humans. Anatomic, histologic, physiologic, and immunologic species-related differences probably make the ratite heart unsuitable for transplantation into humans. © Munksgaard, Copenhagen.