Oxidative stress plays a major role in the pathogenesis of interstitial lung diseases. The antioxidant enzymes glutathione S-transferases (GST) and manganese superoxide dismutase (MnSOD) are important components of lung defence against oxidative stress, and polymorphisms in the genes which regulate their expression may represent important disease modifiers.A matched case-control study was conducted to determine the influence of the GSTP1, GSTT1 and MnSOD polymorphisms on susceptibility to progressive massive fibrosis (PMF). Seven hundred ex-coal miners were included in the study; 350 were classified as PMF cases while 350 with a similar underground mining tenure but no clinical or histological evidence of lung disease served as controls. Genotype analysis was performed on genomic DNA, using a 5' nuclease PCR assay.None of the individual investigated polymorphisms and two-way gene-gene interactions had a statistically significant association with PMF.The results of this study suggest that polymorphic genotypes within the GST gene cluster and MnSOD do not affect individual susceptibility to PMF.