Glutathione-S-transferases (GSTM1 and GSTP1) and nicotinamide quinone oxidoreductase (NQO1) genes play an important role in cellular protection against oxidative stress which has been linked to asthma pathogenesis. We investigated whether common, functional polymorphisms in GSTM1, GSTP1 and NQO1 influence airway hyperreactivity (AHR) and atopy among schoolchildren in South Africa. Genomic DNA was extracted from 317 primary schoolchildren, aged 9-11 years, from urban, low socioeconomic communities of Durban, South Africa. GSTM1 (null vs. present genotype), GSTP1 (Ile105Val; AA → AG + GG), and NQO1 (Pro/187Ser; CC → CT/TT) genotypes were determined using polymerase chain reaction (PCR) methods. Atopy was defined as a positive skin-prick test to any of several common allergens. Airway hyperreactivity (AHR) was evaluated by pulmonary function testing before and after methacholine challenge. Among the children, 30% were GSTM1 null, 65% carried the G allele for GSTP1, and 36% carried the C allele for NQO1. The frequency of GSTM1, GSTP1, and NQO1 variants among our South African sample was similar to frequencies found in similar ethnic groups worldwide. Marked airway reactivity (PC(20) ≤ 2 mg/ml) was found in 10.3% of children and approximately 40% of them were atopic. No significant associations for GSTM1 and NQO1 with either AHR or atopy were identified. A significant protective effect against atopy was found among children with one or two copies of the GSTP1 G allele.