Notes: Background Polymorphisms at the glutathione S-transferase (GST) P1 locus were associated with asthma-related phenotypes and bronchial hyper-responsiveness.Objective This study investigated whether GSTP1 genotypes and outdoor air pollution were interactive risk factors on childhood asthma.Methods Four hundred and thirty-six subjects were recruited for oral mucosa samplings from 2853 fourth- to ninth-grade schoolchildren from three districts with different air pollution levels in southern Taiwan. PCR-based assays were performed by oral mucosa DNA to determine GSTP1 genotypes. We also conducted a nested case–control study comprising 61 asthmatic children and 95 controls confirmed by International Study of Asthma and Allergies in Childhood questionnaire results and methacholine challenge test. Multiple logistic regression was used to adjust for potential confounding factors.Results All participants were homozygous at the Ala-114 locus. Although only a marginally significant association existed between the frequency of homozygosity at the Ile-105 locus and asthma when air pollution was not considered, we found a significant gene–environmental interaction between GSTP1–105 alleles and air pollution after adjusting for confounders (P=0.035). Specifically, we found that compared with participants carrying any Val-105 allele in low air pollution, those who are Ile-105 homozygotes in high air pollution district had a significantly increased risk of asthma (adjusted odds ratio (AOR)=5.52, 95% confidence interval (CI)=1.64–21.25). Compared with participants carrying any Val-105 allele, in high air pollution district, children with Ile-105 homozygotes had a significantly increased risk of asthma (AOR=3.79, 95% CI=1.01–17.08), but those who carried two Ile-105 alleles in low or moderate air pollution districts did not show similar tendencies. The risk of asthma also revealed a clear dose–response relationship with outdoor air pollution in children with Ile-105 homozygotes.Conclusion Our result suggests a gene–environmental interaction between GSTP1–105 genotypes and outdoor air pollution on childhood asthma.