Immunological tolerance of systemic immunity can be induced by the oral administration of an exogenous antigen, which is termed oral tolerance. We examined whether there was a difference in the degree of tolerance between individual antigenic determinants in oral tolerance. Feeding bovine alpha s1-casein, a major protein in cow's milk, as a constituent of the diet induces oral tolerance in mice. However, a weak antibody response can be elicited in the alpha s1-casein-fed animals by subsequent immunization with the antigen. We examined the fine specificity of such anti-alpha s1-casein antibodies produced in alpha s1-casein-fed mice. The results demonstrated that there was a difference in the inhibition of antibody response between different B cell determinants. Differential inhibition could also be observed for T cell responses. T cells specific for dominant determinants were preferentially tolerized, while those for cryptic determinants escaped oral tolerance. Our results imply the importance of antigen presentation for this differential inhibition of antigenic determinants. We suggest that orally administered antigen does not induce tolerance to some of the B and T lymphocyte repertoire which could potentially induce harmful food hypersensitivity.