There is considerable interest in the design of approaches that will permit the accurate identification and characterization of proteins that have the inherent potential to induce sensitization and cause food allergy. Among the methods used currently as part of such assessments are consideration of structural similarity to, or amino acid sequence homology with, known human allergens; whether there exists immunologic cross-reactivity with known allergens; and measurement of resistance to proteolytic digestion in a simulated gastric fluid. Although such approaches provide information that will contribute to a safety assessment, they do not--either individually or collectively--provide a direct evaluation of the ability of a novel protein to cause allergic sensitization. For this reason, work is in progress to design and evaluate suitable animal models that will provide a more holistic assessment of allergenic potential. In this laboratory, the approach we have taken has been to examine the characteristics of immune responses induced in mice following parenteral (intraperitoneal) exposure to test proteins. The basis of this method is to determine simultaneously the overall immunogenic potential of proteins [measured as a function of immunoglobulin (Ig) G antibody responses] and to compare this with their ability to provoke IgE antibody production, IgE being the antibody that effects allergic sensitization. Although this approach has not yet been evaluated fully, the results available to date suggest that it will be possible to distinguish proteins that have the inherent potential to induce allergic sensitization from those that do not. In this article we summarize progress to date in the context of the scientific background against which such methods are being developed.