We previously reported that the infusion of certain soluble immune complexes stimulated mucus release from the rat small intestine in vivo. The present studies sought to evaluate the response of the intestine of normal and immunized rats to the infusion of antigen alone. One hour after the intraduodenal infusion of antigen, small intestinal washings were obtained and analyzed for the presence of 35S-labeled, high m.w. glycoprotein of goblet cell origin. The amount of goblet cell glycoprotein released was estimated from the radioactivity present in the void volume of a Sepharose 4B gel filtration column. The release of goblet cell mucus was enhanced by antigen stimulation in orally immunized animals. The discharge of goblet cell mucus was not increased after antigen infusion in animals immunized by the i.p. route despite the induction of high levels of serum antibody. The inability to demonstrate release of mucus after antigen challenge in systemically immunized rats suggests that the amount or the type(s) of antibody required at the mucosal surface is produced only after oral immunization.