Allergic diseases are multifactorial; they develop from complex interactions between genes and the environment. The immunological bias toward atopy and asthma might be established during in utero development of the fetal immune system. We prospectively investigated the association between maternal cytokine changes during pregnancy and the development of childhood wheezing and atopy at three years of age. Blood samples from 90 pregnant women were assayed for TNF-alpha, TGF-beta, IFN-gamma, IL-4, IL-6, and IL-2 at 18 weeks of gestation and at 6 weeks after delivery. Telephone interviews were performed and a questionnaire administered to assess wheezing and allergic disease in the children. The serum total IgE and specific IgE to eggs, milk and dust mites were measured. Maternal IFN-gamma, TNF-alpha and TGF-beta levels significantly decreased during pregnancy compared to the levels after delivery. However, the IL-4 levels did not change. Maternal TNF-alpha and IFN-gamma levels were decreased both before and after delivery in children with reported wheezing. Individual maternal IL-4 levels, before delivery, were higher than after delivery in the children that developed wheezing. There were no significant differences in maternal cytokine levels between children with and without asthma. In children with atopy, the maternal IFN-gamma /IL-4 ratio, during the first trimester, had a tendency to decrease compared to the children without atopy, whereas the maternal IL-2 levels at 6 weeks after delivery were increased. A first pregnancy showed higher concentrations of IL-4 before and after delivery than did women with multiple pregnancies. Maternal cytokine levels begin to change toward a Th2 immunity starting in the first trimester. A stronger Th2 immune response during the first trimester of pregnancy is associated with childhood wheezing and atopy at three years of age, and a first pregnancy.