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Background. The glutathione S-transferase enzymes (GSTs) play an important role in the detoxification of environmental tobacco smoke (ETS), which contributes to airway inflammation, a key component of asthma. Genetic variation in GST genes may influence individuals' ability to detoxify environmental pollutants. Objective. To examine the role of polymorphisms in GSTP1 (Ile105Val and Ala114Val), alone and in combination with ETS exposure, on atopy and asthma severity. Methods. GSTP1 Ile105Val and Ala114Val were genotyped and ETS exposure was assessed by parental questionnaire, which was validated by urinary cotinine measurements. Associations between ETS exposure, GSTP1 polymorphisms, and their interaction on atopy and asthma severity were investigated. Results. For the functional GSTP1 105 SNP, those with the Ile/Ile genotype had odds for atopy of 2.77 ( p = .054) when assessed by genotype alone, which increased to 9.02 ( p = .050) when ETS was included, relative to individuals with other genotypes. Likewise, compared to children with other GSTP1 114 genotypes, those with Ala/Ala genotype had a 5.47-fold ( p = .002) increased risk of atopy ( p = .020) when assessed by genotype alone, increasing to 9.17-fold when ETS was included. The 105 Ile/Ile individuals all had the AA (105 Ile/Ile and 114 Ala/Ala) haplotype group; therefore, the odds for atopy were the same. Individuals without any *C haplotype (105 Val and 114 Val allele) who were exposed to ETS had a 9.17-fold increased risk of atopy when compared with individuals with at least one *C haplotype and not exposed to ETS ( p = .020). Conclusion. There were significant interactions between GSTP1 SNPs, atopy, and ETS exposure in this cohort. [ABSTRACT FROM AUTHOR]