Background: According to data from animal and in vitro studies, transforming growth factor-β (TGF-β) has a crucial effect on 2 essential parts of the mucosal immune system: IgA production and oral tolerance induction. Objective: We sought to ascertain whether TGF-β in breast milk is associated with specific IgA production and atopic disease in human subjects. Methods: Forty-seven infants with several atopic family members were followed during their first year of life. The concentrations of TGF-β1 and TGF-β2 in maternal colostrum, mature milk, and the infants’ sera were determined. The enzyme-linked immunospot assay was used to assess the infants’ specific IgA production in response to β-lactoglobulin, casein, gliadin, and ovalbumin. Results: At 12 months, atopic dermatitis was confirmed in 29 of 47 infants; in 11, atopic disease had begun during exclusive breast-feeding (preweaning onset), whereas in 18 the disease manifested itself after weaning (postweaning onset). The concentrations of both TGF-β1 and TGF-β2 were higher in maternal colostrum, but not in mature milk and infants’ serum, in infants with postweaning-onset atopic disease compared with those with preweaning-onset disease (P = .0008 and P = .015, respectively). The concentration of TGF-β2 was, and that of TGF-β1 tended to be, higher in the colostrum of mothers whose infants had specific IgA-secreting cells at 3 months in response to at least one of the dietary antigens tested compared with those who did not have such cells (P = .048 and P = .076, respectively). Conclusion: TGF-β in colostrum may prevent the development of atopic disease during exclusive breast-feeding and promote specific IgA production in human subjects. (J Allergy Clin Immunol 1999;1251-7.)