Mucosal and systemic (serum) immune responses were studied after oral, anal or intramuscular ( i m ) immunization with particulate (Vibrio anguillarum) or soluble (ferritin) antigen. Antigenspecific antibodies were found by ELISA in skin mucus after repeated oral or anal administration of bacteria, but not after immunization with ferritin. Daily feeding with bacteria did not give detectable antibodies in serum, while regular oral administration of ferritin resulted in an increase of specific antibodies during the first 3 weeks. From that time immunosuppression was observed, as the antibody titre decreased despite the continued ferritin feeding. Immunosuppression was also found after a second anal intubation or i.m. injection with ferritin, independent of the route of priming(i.m. or anal). On thecontrary, asecondanalintubationofbacteriaresultedinasecondary serum response. Theseresultscombined withthosereportedin PartsIandIIofthestudyindicatean important immunological role for the second gut segment. Because mucosal as well as serum responses can be obtained by anal immunization with bacteria, the significance for oral vaccination is discussed.