BACKGROUND: Glutathione S-transferase (GST) enzymes are critical for detoxifying reactive oxygen species (ROS) and their products which have been implicated in the pathology of inflammatory diseases such as atopic dermatitis (AD). METHODS: We investigated the effects of genetic polymorphisms of GST on the risk of AD in preschool age children. Biomarkers for oxidative stress were also evaluated with respect to GST genotype. RESULTS: The GSTP1 Val105 allele was significantly associated with an increased risk of AD [odds ratio (OR)=1.62, p<0.05]. The combination of the GSTP1 Val105 allele and the GSTT1 null genotype further increased this risk by 2.3-fold (p<0.01). No association was observed for the GSTM1 null or GSTT1 null genotype alone. In children with AD, blood total antioxidant capacity was significantly less (p<0.001), while malondialdehyde was higher (p=0.12). Children with the GSTP1 Val105 allele had significantly lower concentrations of erythrocyte glutathione compared to GSTP1 ILE/ILE homozygotes (P=0.03). CONCLUSIONS: Our study suggests that the GSTP1 Val105 allele is an important determinant of susceptibility to AD in preschool age children and increased oxidative stress may play a role in the pathogenesis of AD.