BACKGROUND:: OBJECTIVE:: METHODS:: Five hundred sixty and 49 children of parents with and without allergic disease or asthma, respectively, were enrolled into a prospective birth cohort study (Urban Environment and Childhood Asthma). Cord blood mononuclear cells were incubated with innate and adaptive immune stimuli, and cytokine responses (ELISA) were compared with season of birth, parental characteristics, in utero stressors, and fetal growth. RESULTS:: Many cytokine responses varied by season of birth, including 2-fold to 3-fold fluctuations with specific IFN-α and IFN-γ responses. Birth weight was inversely associated with IFN-γ responses to respiratory syncytial virus (R = −0.16), but positively associated with IL-8 responses to a variety of innate stimuli (R = 0.08–0.12). Respiratory syncytial virus–induced cytokine responses were 21% to 54% lower in children of mothers with asthma. Cytokine responses were generally lower in babies born to parents with allergy/asthma. CONCLUSIONS