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A possible solution to the chronic shortage of allografts is xenotransplantation, the use of tissue from an animal donor. Most experts believe that the pig will provide the most suitable solid organs for use in human beings. Although porcine organs are rapidly rejected by a process called hyperacute rejection (HAR), there is hope that several novel therapeutic strategies, already tested in animal models, will overcome this hurdle in patients. Successful clinical trials of these strategies, expected within the next few years, may herald the era of clinical xenotransplantation. However, there is increasing evidence that other barriers, both immune and non-immune, might exist to limit the survival of xenografts beyond the HAR phase. New strategies to overcome these barriers will be needed if long-term xenograft survival equivalent to, or better than, that of allografts is ever to be achieved.