The critical histologic review of our experience with small bowel allotransplantation in the dog is presented. While "classical" rejection with dense small cell infiltration and mucosal destruction does occur, more common is the "atypical" rejection reaction in which cellular infiltration is sparse. This "atypical" rejection was characterized by a significant decrease of mucosal epithelial structures with increased mitotic figures in crypt cells and frequent vascular changes, including segmental fibrinoid necrosis and thrombosis with or without overlying mucosal destruction. Substantial regenerating capacity of bowel mucosa tends to compensate for the destruction, complicating the histology. The host lymph nodes and spleen present a histologic picture highly suggestive of GVH reaction. The reduction in host lymphocytes in these organs from karyorrhexis with replacement by histiocytes and subsequently by plasma cells is described. It is emphasized that rejection and GVH are not mutually exclusive and occur simultaneously. The decrease of functional mucosal mass could well account for the nutritional malsequelae. Also, the weakening of immune structures on the host and the graft side may predispose to catastrophic enterogenous infections, perhaps explaining the large number of animals that die without overt signs of rejection following small bowel transplantation.