The induction of oral tolerance by oral immunization has been well recognized. Accumulated evidence shows that oral tolerance can be mediated by orally activated humoral and cellular factors. In animal models, the development of several T cell-mediated autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, uveitis and diabetes type 1 can be inhibited by oral immunization of the respective antigens. In allergy, oral administration of certain allergens can prevent and reduce both contact and atopic dermatitis. Oral tolerance to alloantigen also reduces graft rejection. In spite of these encouraging results, the usefulness of this approach for an alternative immunotherapy in humans needs to be investigated further.