Oral immunization of an animal is generally hard to achieve unless large quantities of antigen are administered. In this study a number of antigens were tested for their ability to elicit a systemic immune response upon oral administration. It was found that bacterial pili, LTB, lectins, and a viral hemagglutinin were all able to elicit significant antibody titers upon oral feeding. The immune response thus generated to LTB and K99 pili could be completely abolished by cofeeding a number of sugars that have close structural homology to the terminal sugars of the GM1 and GM2 gangliosides to which these molecules are known to bind. All of the proteins that were active in oral immunization are known to possess "lectin or lectin-like" binding activities. It is therefore proposed that these molecules are able to bind to glycolipids and glycoproteins on the intestinal mucosa and to stimulate these cells to transport the proteins into the systemic circulation, thereby eliciting a systemic immune response. Molecules that did not possess this binding activity were unable to elicit significant responses at the doses tested.