Chronic, isolated, ileal (Thiry-Vella) loops in rabbits have been used to study the role of Peyer's patches in the local immune response of the intestine to live, locally invasive bacteria. Three weekly doses of Shigella X16 were administered to these isolated loops and the IgA and IgG activity against shigella were measured in samples of sera and loop secretions by using an enzymelinked immunoassay technique. Secretions from loops containing a Peyer's patch exhibited a stronger early IgA response to the bacteria than did secretions from loops lacking a Peyer's patch. The enhanced early local immune response in loops containing a Peyer's patch may reflect more efficient processing of the antigen by the specialized follicle-associated epithelium that overlies Peyer's patches, or it may be a result of the increased chance of an antigen encountering immunocompetent cells among the large number of lymphocytes in the Peyer's patch. However, IgA against the bacteria in later fluids from both types of loops were comparable. the local immunity achieved in loops lacking a Peyer's patch may have resulted from local invasion of the epithelium with stimulation of lymphocytes in the lamina propria, or bacterial antigens may have been brought to mesenteric lymph nodes for processing. Alternatively, if small isolated lymphoid follicles (which are present throughout the intestine although not visible without histologic examination) have functional capabilities similar to those of Peyer's patches, they may play a role in the response seen in secretions from both types of loops. Clearly, Peyer's patches are important structures, but it is still unknown whether they can exert some unique influence on the local immune response of the gut, or whether they have gained eminence over smaller intestinal lymphoid structures by virtue of their prominence.