Background: Breast milk contains immune factors that compensate for the underdeveloped defenses of the gut of the newborn infant. Objective: Ne sought to study the importance of these factors in the immune responses of infants with cows' milk allergy (CMA) to the proteins in cows' milk (CM). Methods: We prospectively followed the development of CMA in 6209 healthy infants and collected samples of colostrum from mothers. Samples from mothers of infants with CMA and from control subjects were analyzed for immunoglobulins, CM-specific antibodies, and cytokines. In infants with CMA,: correlations between the concentration of transforming growth factor (TGF)-beta 1 in colostrum and the extent of the immune response to Chi proteins were studied. Results: The concentration of TGF-beta 1 in colostrum samples from mothers of infants with IgE-mediated CMA (n = 65) was lower (mean, 589 pg/mL; 95% confidence interval [CI], 413-840) than from mothers of infants with non-IgE-mediated CMA (n = 37; mean, 1162 pg/mL; 95% CI, 881-1531; t = 2.57, P = .012). In 126 control subjects the mean concentration was 807 pg/mL (95% CI, 677-963), In the infants with CMA (n = 96-100), the concentration of TGF-beta 1 in colostrum was positively correlated with IgA antibodies to beta-lactoglobulin and IgG antibodies to alpha-casein and whole formula and negatively with the diameter of a skin prick test response to CM and lymphocyte stimulation indices to alpha-casein and beta-lactoglobulin. Conclusions: In an infant prone to having CR-LA, the TGF-beta 1 content of mother's colostrum may promote IgG-IgA antibody production and inhibit IgE- and cell-mediated reactions to CM.