Chronic obstructive pulmonary disease (COPD) is a complex combination of signs and symptoms in patients with chronic bronchitis and emphysema, diseases that largely result from cigarette smoking. A little information is available for the underlying molecular mechanisms that are responsible for its occurrence. Polymorphisms in genes of xenobiotics metabolizing enzymes are expected to modulate individual responses to genotoxic carcinogens. Present study was a case-control study of COPD patients and healthy controls. Genetic polymorphisms of GSTM1 and GSTT1 genes in 50 COPD patients and 50 healthy controls were investigated using multiplex polymerase chain reaction-restriction fragment length polymorphism techniques to determine whether polymorphisms of these genes are linked to genetic susceptibility to COPD. All subjects were males and smokers. The frequency of GSTM1 homozygous null genotype was 28.0% in COPD cases when compared with controls (32.0%). The difference was not significant showing that risk of COPD was not associated with the GSTM1 null genotypes. The frequencies of homozygous null genotypes of GSTT1 were significantly higher in COPD cases as compared with controls (40% versus 14.0%) suggesting that the theta-glutathione S-transferases null genotype may be associated with the susceptibility to COPD. No significant differences were observed when comparisons were performed according to severity of disease and smoking for GSTM1 and GSTT1. It was also observed that COPD developed in the early age and with a shorter pack-year history in Indian population.