Background: By resisting digestion in the stomach, the major bovine milk allergen, @-lactoglobulin, is believed to act as a transporter of vitamin A and retinol to the intestines. fl-Lac- toglobulin has 2 intramolecular disultide bonds that may be responsible for its allergic effects.Objective: This study was carried out to assess the importance of disultide bonds to the allergenicity and digestibility of p-lac- toglobulin.Methods: P-Lactoglobulin was subjected to reduction by the ubiquitous protein thioredoxin, which was itself reduced by the reduced form of nicotinamide adenine dinucleotide phos- phate by means of nicotinamide adenine dinucleotide phos- phate-thioredoxin reductase. Digestibility,was measured with a simulated gastric fluid; results were analyzed by SDS-PAGE. Allergenicity was assessed with an inbred colony of high IgE-producing dogs sensitized to milk.Results: As found for other proteins with intramolecular disul- fide bonds, P-lactoglobulin was reduced specifically by the thioredoxin system. After reduction of one or both of its disul- fide bonds, /34actoglobulin became strikingly sensitive to pepsin and lost allergenicity as determined by skin test responses and gastrointestinal symptoms in the dog model. Conclusion: The results provide new evidence that thioredoxin can be applied to enhance digestibility and lower allergenicity of food proteins. 