Small bowel transplantation (SBT) is thought to be the only radical treatment for short bowel syndrome in childhood. It is very important that the length of the graft and the type of intestine be chosen carefully because this will determine the outcome of transplantation. This model of short bowel syndrome in the rat confirms that total intestinal resection results in malnutrition and failure to gain weight. After 10 cm of ileum was transplanted orthotopically in a syngeneic combination in rats with total intestinal resection, the animals gained weight. The authors determined that 10 cm of terminal ileum is the minimum length required for survival. Second, the immunologic basis of lethal graft-versus-host reaction (GVHR) as it relates to the intestinal graft length was also evaluated. Ileal grafts of 10 cm from LEW (RT1l) rats were implanted heterotopically into (LEW x BN)F1 rats. Ileal grafts of 10 or 40 cm were implanted from BN(RT1n) rats into (LEW x BN)F1 animals. A lethal GVHR always occurred after grafting a 10 cm ileum in the LEW/F1 combination, whereas only 17% of the BN/F1 recipients died of typical GVHR. However, in the latter combination, 67% lethal GVHR was induced when 40 cm of the intestinal graft was implanted. These results indicate that mesenteric lymph nodes are a major source of lethal GVHR, but gut-associated lymphoid tissue can also induce this.