Background: Allergen-specific T cells play an important role in the allergic immune response to various environmental allergens. In vitro studies have shown that T-cell responses to these allergens do occur prenatally. Some allergens (milk proteins) appear to lead more often to fetal T-cell priming than others (house dust mite allergen, ovalbumin, and birch and grass pollen allergens). Objective: We sought to determine the window of opportunity for prenatal T-cell priming with inhalant and nutritive allergens. Methods: The T-cell reactivity of cord blood cells derived through cordocentesis from unborn (n = 62) and term babies (n = 114) in response to inhalant allergens (birch pollen major allergen, recombinant Bet v 1, and timothy grass major allergen, recombinant Phl p 1) was investigated. Results: The results demonstrate that allergen-specific T-cell reactivity is as common in preterm as in term infants (Bet v 1, 8% and 5%, respectively; Phl p 1, 20% and 25%, respectively). Conclusions: Our data support the hypothesis that differential handling of the allergenic proteins by the feto-placental barrier and possibly by antigen-presenting cells may directly modulate the ensuing T-cell immune response. (J Allergy Clin Immunol 2000;106:530-6.)