Background: Detoxification genes are potential candidates in the susceptibility of patients with chronic obstructive pulmonary disease. Polymorphisms in these genes alter the metabolism of xenobiotics such as present in cigarette smoke. Methods: We conducted a case-control study to investigate total 9 polymorphisms of CYP2E1, CYP2D6 and NAT2 genes by PCR-RFLP. Results: The - 1053C/T and - 1293G/C promoter polymorphisms of CYP2E1 were found to be in complete linkage disequilibrium (LD) (D′ = 1.00, r2 = 1.0, p < 0.0001), whereas - 1293G/C and 7632T/A polymorphisms of the same gene were also in significant LD (D′ = 0.5183, r2 = 1.0, p = 0.01) in patients. The patients over-represented the - 1293GC+CC genotypes of - 1293G/C polymorphism of CYP2E1 (p = 0.03) and NAT2*4/7, NAT2*5/6, NAT2*5/7, NAT2*6/6 and NAT2*6/7 genotypes of NAT2 (p = 0.01, p = 0.039, p = 0.01, p = 0.032, p = 0.006, respectively), resulting in to higher frequency of - 1293C (OR = 7.02, 95% CI = 1.63-30.15, p = 0.002), NAT2*6 (OR = 1.90, 95% CI = 1.27-2.83, p = 0.001) and NAT2*7 (OR = 2.91, 95% CI = 1.65-5.12, p = 0.0001) alleles. The 7632T/A and 9893C/G polymorphisms of CYP2E1 and 1934G/A polymorphism of CYP2D6 did not associate with the disease (p > 0.05). The haplotypes - 1293G:9893C and - 1293G:7632T:9893C were under-represented (p < 0.001), whereas haplotypes - 1293C:7632T, - 1293C:9893C, - 1293C:9893G and - 1293C:7632T:9893C of the 4 CYP2E1 polymorphisms were over-represented in patients (p < 0.05). Conclusion: The CYP2E1 and NAT2 variants associated with COPD. © 2007 Elsevier B.V. All rights reserved.