Foods produced through agricultural biotechnology are reaching the consumer marketplace. These novel foods should be assessed for their safety, including their potential allergenicity. Agricultural biotechnology involves the introduction of novel proteins into the modified foods, and proteins can be allergenic. The potential allergenicity of the introduced proteins can be evaluated by focusing on the source of the gene, the homology of the newly introduced protein to known allergens, the reactivity of the novel protein with IgE antibodies from the serum of individuals with known allergies to the source of the transferred DNA or to materials that are broadly related to the source of the transferred DNA, the resistance of the novel protein to pepsin, and the immunoreactivity of the novel protein in appropriate animal models. Additional factors, such as the level of expression of the novel protein in the modified food and expression in the edible portion of the food, may also yield valuable insights. Applying such criteria provides a reasonable approach to determining whether or not the novel protein is likely to become an allergen.