Background: Several cross-reactive allergens are now known to be involved in the defense responses of higher plants. Such proteins are drawing the attention of plant breeders because of their antimicrobial or stress-alleviating activities. Plants genetically modified to express defense-related proteins are being developed. The current concern is focused on the allergenicity of these intentionally expressed proteins. Objective: It is believed that food allergens are proteins resistant to digestion. Digestibility tests have been accepted as an appropriate method for evaluating the allergenicity of newly introduced proteins. In this study we investigated the usefulness of this method for detecting allergens from natural rubber latex and vegetable foods. Methods: Proteins were extracted from rubber latex, potato, and 5 kinds of fruits. Simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were used for the digestibility test. An aliquot of each digest was periodically withdrawn and analyzed. Allergens were detected with pooled sera from individuals with latex allergy or patients given a diagnosis of oral allergy syndrome. Results: Most latex and vegetable food proteins were digested by the SGF within 4 minutes. Numerous allergens were also decomposed by the SGF within 8 minutes. Although vegetable food allergens were relatively stable in the SIF, kiwi allergens were substantially degraded by the SIF within 16 hours. Conclusion: The pronounced lability of the plant-derived allergens was thought to reflect the discrete sensitization and elicitation processes of patients with latex-fruit syndrome or oral allergy syndrome. These results indicate that the allergenicity of a newly expressed protein should be carefully evaluated according to not only its digestibility but also other important properties. (J Allergy Clin Immunol 2000;106:752-62.)