Background: The evidence that both genes and environment playetiologic roles suggests that the increase in atopic dermatitis (AD)prevalence is likely to involve changes in specific exposures among thepopulation of genetically susceptible individuals. Objective: The purpose of this study was to evaluate the effect of Glutathione S-transferase (GST) genotypes polymorphisms and gestational smoke exposure on pediatric AD on the basis of the cord blood cotinine. Methods: We recruited 261 mother and newborn pairs in 2004. Cordblood and information on perinatal factors of children were gathered atbirth. At 2 years of age, information about development of AD and environmental exposures were collected. We compared AD with non-AD children for GTM1 and GSTP1 polymorphisms stratified by the cotinine level. Multiple logistic regressions were performed to estimate the association of genotypes polymorphisms and cotinine levels with AD. Results: The risk of AD was found to increase with cord blood cotinine levels in a dose-response manner (p for trend 5 0.02). GSTM1 null andGSTP1 Ile/Ile genotypes showed a significant increase in the risk of AD with OR (95%CI) of 3.61 (1.40–9.31) and 3.11 (1.30–7.46) respectively.In children with cotinine level , 0.1 ng/ml, the risk of AD increased for those carrying two GSTP1 Ile-105 alleles (OR 5 6.63, 95%CI1.46–30.18). In children with cotinine level $ 0.1 ng/ml, GSTM1 null genotype was significantly related to AD (OR 5 5.21, 95%CI1.32–20.58).Conclusion: Genetic polymorphism in GSTM1 and GSTP1 may be responsible for children differences in susceptibility to AD with regard to gestational smoke exposure.