The characteristic unresponsiveness of gut-associated lymphoid tissue (GALT) to orally administered antigen has hampered studies of mucosal immunity and the development of effective vaccines to control diseases of mucosal organs. Our previous studies have shown that priming by the intraperitoneal route can overcome this unresponsiveness and enables a vigorous IgA antibody-containing cell (ACC) response from GALT to subsequent intraduodenal (ID) antigen challenge. However the involvement of a concomitant systemic response arising from intraperitoneal priming complicates the analysis of the mucosal component of this response. The studies reported here indicate that immunization of a single Peyer's patch (PP) by subserosal deposition of antigen adjacent to the patch primes for an equivalent IgA ACC response following ID challenge and immunization of multiple PP generates a substantial IgA ACC response in the gut lamina propria even in the absence of luminal challenge. This response persists for at least 84 days. These techniques provide a means by which the requirements for induction of IgA responses can be studied in the absence of a response in systemic lymphoid tissue.