Cholera toxin (CT) has been shown to be a most potent mucosal immunogen and an adjuvant to orally administered unrelated antigens. We investigated the effect of the oral administration of substances with the ability to bind to intestinal epithelial cells on the immune responses against themselves in the presence or absence of CT. Mice were fed non-specific rabbit IgG (RGG) or rabbit IgG (a-GA1) specific to asialo GM1 glycolipid, a major component of the apical membrane of mouse small intestinal epithelial cells, with or without CT. Oral administration of a-GA1 evoked stronger antibody responses than that of RGG in both the serum and intestinal fluid in the presence of CT. However, when the antigens were administered singly without CT, no significant antibody response was detected. In this case, oral administration of RGG induced severe suppression of the systemic antibody response to a subsequent intraperitoneal injection of RGG. In contrast, a-GA1 could not induce oral tolerance. Together these findings suggest that substances with the ability to bind to intestinal epithelial cells are strong immunogens in the presence of CT and weak tolerogens in the absence of CT.