We have studied the T-cell-mediated response to the major allergen of cow’s milk, in a group of newborns at risk of developing cow’s milk allergy, and in a control group. Before any atopic status has developed, we observe β-lactoglobulin-specific primary proliferation only in the group at risk for food-related allergies. In this group, the capability to proliferate is not due to placental transmission of ‘factors’ from allergic mothers. The recognition of the tested β-lactoglobulin peptides does not show major differences between the responder and nonresponder populations. In the responder population, the response to p145–161 appears linked to a primary response to ovalbumin, another frequent food allergen. On the basis of our findings, we propose a model in which development of allergic diseases is linked to an alteration of T-cell activation through the engagement by the antigen; the HLA phenotype determines the allergen(s) involved, and other genetic or environmental factors dictate the clinical characteristics of the disease.