Reduced particulate matter (PM10) exposure attenuated the age-related lung function decline in our cohort particularly in the small airways (FEF25-75). We hypothesized that polymorphisms in glutathione S-transferase (GST) and heme oxygenase-1 (HMOX1) genes, important for oxidative-stress defense, modify these beneficial effects.A population-based sample of 4365 adults was followed up 11 years including questionnaire, spirometry, and DNA blood sampling. PM10 exposure was estimated by dispersion modeling and temporal interpolation. Main effects on annual decline in FEF25-75 and interactions with PM10 reduction were investigated for polymorphisms HMOX1 rs2071746 [T/A], rs735266 [T/A], and rs5995098 [G/C], HMOX1 (GT)n promoter repeat, GSTM1 and GSTT1 deletions, and GSTP1 p.Ile105Val using mixed linear regression models.HMOX1 rs5995098, HMOX1 haplotype TTG and GSTP1 showed significant genetic main effects. Interactions with PM10 reduction were detected: a 10microg.m(-3) reduction significantly attenuated annual FEF25-75 decline by 15.3 mL.s(-1) only in absence of HMOX1 haplotype ATC. Similarly, carriers of long (GT)n promoter repeat alleles or GSTP1 Val/Val genotype profited significantly more from a 10microg.m(-3) reduction (26.5 mL.s(-1) and 27.3 mL.s(-1) respectively) than non-carriers.Benefits of a reduction in PM10 exposure are not equally distributed across the population but are modified by the individual genetic make-up determining oxidative stress defense.