The need for widely accepted and validated animal models to test the potential allergenicity and potency of novel (biotechnology-derived) proteins has become an important issue for their safety evaluation.In this article, we summarize the results of the development of an oral sensitization protocol for food proteins in the rat. Young Brown Norway rats were exposed to either various purified allergenic proteins (e.g., ovalbumin, partly purified), a whole food (cow's milk), or total protein extracts (hen's egg white, peanut) by daily gavage dosing during 42 days without the use of an adjuvant. The results showed that Brown Norway rats can be sensitized orally to the various allergenic food proteins tested, resulting in antigen-specific immunoglobulin (Ig) G and IgE responses, without the use of adjuvants. Animals orally exposed to cow's milk or total protein extracts of egg white also developed specific IgE and IgG antibodies that recognized the same proteins compared with antibodies from patients allergic to egg white or cow's milk. We also studied local and systemic immune-mediated effects. In ovalbumin-sensitized rats, some clinical symptoms of food allergy were studied upon an oral challenge with ovalbumin. The results demostrated that gut permeability was increased and that in some animals breathing frequency and systolic blood pressure were temporarily decreased. The results obtained show that the Brown Norway rat provides a suitable model for food allergy research and for the study of relative allergenicity of existing and novel food proteins.