&NA;Results from a recent clinical trial have suggested that the feeding of autoantigenic proteins may be an effective therapy for autoimmune diseases (Weineret al., Science1993, 259:1321‐1326). This treatment, called oral tolerance therapy, proposes to inhibit aberrant immune responses by producing immune “acceptance” or tolerance to target tissue proteins. Because of the innovative nature of this approach, interest has been focused on the regulatory mechanisms that produce the state of oral tolerance. In this review, we address the models of oral tolerance and suggest that this state may involve unique regulatory mechanisms based on the amount of fed protein antigen.Current Opinion in Gastroenterology 1993,9:981‐985