The prevalence of asthma and related allergic disorders has increased considerably over the last 25 years. Because genetic stock has not changed, environmental factors must have influenced the phenotype. Infants who experience the development of allergy already have an altered immune response at birth. We have investigated the development of immune responses during gestation and the effect of maternal allergen exposure during pregnancy and infant exposure in the first month of life on the development of allergy and disease. There was higher specific peripheral blood mononuclear cell proliferation to house dust mite and birch pollen in the third trimester compared with the second trimester, with the first positive responses seen at 22 weeks gestation. Maternal exposure to birch pollen after 22 weeks resulted in higher infant peripheral blood mononuclear cell responses to birch pollen at birth. Infants born at term, with at least 1 atopic parent with asthma, who experienced the development of allergic symptoms and positive skin prick test by 1 year of age had raised proliferative responses to house dust mite at birth compared with those infants with no symptoms. In genetically predisposed individuals, antenatal factors including maternal and thereby fetal exposure to allergens and materno-placental-fetal immunologic interactions are active in determining whether an allergic predisposition is manifested as disease.