We hypothesized that lymphoid organs within intestinal allografts contribute to their immunogenicity. Consistent with this hypothesis recipient T cells rapidly migrated to the lymph nodes and Peyer's patches of syngeneic and allogeneic intestinal grafts such that at 24 h approximately 50% of the lymphocytes isolated from donor lymphoid organs were of recipient origin. However, only in the lymphoid organs of allografts did recipient T cells display an activated phenotype, proliferate and produce IFNgamma. Rejection of allogeneic intestines lacking lymphoid organs was dramatically impaired in splenectomized, lymph node-deficient recipients compared to lymph node bearing, wild-type allogeneic intestines. This demonstrates the important role of donor lymphoid organs in the rejection process. Furthermore, recipient T cells proliferated more extensively and produced more IFNgamma in donor lymphoid organs than in recipient lymphoid organs, indicating that donor lymphoid organs play a dominant role in initiating the recipient anti-donor immune response following intestinal transplantation.